2021 Article 1300

Jami et al.
Translational Psychiatry (2021)11:197

https://doi.org/10.1038/s41398-021-01300-2 Translational Psychiatry
REVIEW ARTICLE Open Access
Parental characteristics and offspring mental health

and related outcomes: a systematic review of
genetically informative literature
Eshim S. Jami1,2, Anke R. Hammerschlag1,3,4, Meike Bartels 1,3
and Christel M. Middeldorp 1,4,5
Abstract
Various parental characteristics, including psychiatric disorders and parenting behaviours, are associated with offspring
mental health and related outcomes in observational studies. The application of genetically informative designs is
crucial to disentangle the role of genetic and environmental factors (as well as gene–environment correlation)
underlying these observations, as parents provide not only the rearing environment but also transmit 50% of their
genes to their offspring. This article first provides an overview of behavioural genetics, matched-pair, and molecular
genetics designs that can be applied to investigate parent–offspring associations, whilst modelling or accounting for
genetic effects. We then present a systematic literature review of genetically informative studies investigating
associations between parental characteristics and offspring mental health and related outcomes, published since 2014.
The reviewed studies provide reliable evidence of genetic transmission of depression, criminal behaviour, educational
attainment, and substance use. These results highlight that studies that do not use genetically informative designs are
likely to misinterpret the mechanisms underlying these parent–offspring associations. After accounting for genetic
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effects, several parental characteristics, including parental psychiatric traits and parenting behaviours, were associated
with offspring internalising problems, externalising problems, educational attainment, substance use, and personality
through environmental pathways. Overall, genetically informative designs to study intergenerational transmission
prove valuable for the understanding of individual differences in offspring mental health and related outcomes, and
mechanisms of transmission within families.
Introduction Thus, observed parent–offspring associations may be wholly

Parents are considered a driving force in the develop- or partially explained by genetic factors shared between the
ment of their children and parental factors are associated parent and child; i.e. in a gene–environment correlation
with various mental health outcomes in offspring, (rGE), when exposure to specific environments depends on
including emotional and behavioural problems1. How- an individual’s genotype. The potential mechanisms
ever, although observed associations between parental (genetic transmission, environmental transmission and
factors and offspring outcomes are often interpreted as gene–environment correlation) underlying associations
direct environmental influences, in truth parents provide between parental characteristics and offspring outcomes are
both the rearing environment and genes to their children. described in detail in Fig. 1. Designs that do not account for
the role of genetic factors in parent–offspring correlations
can lead to biased estimates and erroneous conclusions
Correspondence: Eshim S. Jami ([email protected]) about the extent to which these associations are causal.
1
Department of Biological Psychology, Vrije Universiteit Amsterdam, Genetically informative designs that explicitly model or
Amsterdam, the Netherlands
2 control for potential genetic effects are essential for
Department of Clinical, Educational and Health Psychology, Division of
Psychology and Language Sciences, University College London, London, UK
Full list of author information is available at the end of the article
© The Author(s) 2021

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Jami et al. Translational Psychiatry (2021)11:197 Page 2 of 38
Fig. 1 Mechanisms underlying parent-offspring associations. A figure describing potential mechanisms (genetic transmission, environmental
transmission, and gene-environment correlation) underlying associations between parental characteristics and offspring outcomes.
improving our understanding of the true effect of the par- environment via parentally provided rearing factors,
entally provided environment on offspring mental health. and to a lesser extent, the unshared environment
In genetic epidemiology, the classical twin design is through specific parent–child interactions. Conse-
generally used to decompose the contribution of quently, genetically informative designs that include
genetic and environmental effects underlying human both the parent and offspring generations are required
traits2. Twin-based research shows that most mental to disentangle genetic and environmental effects
health and related traits are moderately heritable (under underlying parent–offspring associations.
the influence of additive genetic effects), with additional The present review aims to synthesise literature inves-
variance explained by the unique environment (which is tigating the association between parental characteristics
specific to each individual), and for some traits also the and offspring mental health and related outcomes in
shared environment (environments that the twins have genetically informative designs. An earlier systematic
in common)3. However, classical twin studies say little review published in 2014 focused on the children-of-twins
about mechanisms of transmission within families method4. However, several novel methodologies that
where, in addition to genetic transmission, parental investigate within-family transmission using innovative
effects may be transmitted through both the shared techniques have emerged in the past few years.
Consequently, there is a gap in the literature for a broad adoption and children-of-twins studies is that they can be
systematic overview that incorporates all genetically used to investigate rGE (Table 1). This is particularly
informative designs that can be applied to study important as even within genetically informative designs,
parent–offspring associations. Here, we focus on studies unmeasured rGE can inflate estimates of genetic or
published from 2014 onwards, as these have not been environmental effects. For instance, if an observed
covered by previous reviews. We first provide a brief parent–offspring association is present in both biological
overview of the types of genetically informative designs and adoptive duos, but the correlation is higher in bio-
that can be employed to investigate parent–child asso- logical (shared genes plus rearing) than adoptive (rearing
ciations. This is followed by a systematic review of studies only) families, this indicates the contribution of both
investigating associations between parental characteristics genetic and environmental effects; i.e. passive rGE. If
and offspring mental health and related outcomes, unaccounted for, this rGE, reflected in increased similarity
including internalising behaviours (such as anxiety and between biological parents and lived-with offspring, could
depression), externalising behaviours (such as attention- potentially lead to an inflated estimation of genetic
deficit/hyperactivity disorder), educational attainment, transmission in adoption studies.
substance use and personality. Due to modern developments in assisted reproductive
technology and the availability of large-scale population-
Genetically informative designs based registers, novel pseudo-adoption designs have
Designs that can be used to separate genetic and emerged that apply the same principles (see adoption and
environmental mechanisms of transmission from parents related designs in Fig. 1) to investigate genetic and
to offspring broadly fall into the following three cate- environmental effects in non-adoption families. Within
gories: behavioural genetics designs, matched-pair assisted conception7 studies, genetically related or
designs, and molecular genetics designs. In this section, genetically unrelated parents are analogous to the biolo-
we summarise the principles underlying these approaches gical and adoptive parents in an adoption design, whereas
(Fig. 2), describe specific methods in detail and discuss in triparental family8 and multiple parenting relation-
their application as well as advantages and disadvantages ships9 designs, the rearing effect of step-parents and
(Table 1). genetic effect of not-lived-with biological parents are
examined (Table 1).
Behavioural genetics designs
Behavioural genetics designs leverage knowledge of Matched-pair designs
relatedness among individuals within a family to make Matched-pair designs strengthen the causal inference of
inferences about the contribution of genetic and envir- an observed parent–offspring association by adjusting for
onmental factors underlying parent–offspring associa- all unmeasured genetic and environmental familial effects.
tions. The adoption5 and children-of-twins4,6 designs (Fig. 2) In sibling comparison10 studies (Fig. 2), a sibling with no
are key tools used to distinguish the effects of genetic and exposure to the parental candidate environment is included
environmental transmission. Associations between biolo- in the analysis as a control, as siblings are naturally mat-
gical parents and their adopted-away offspring suggest ched for shared genes and the family environment. Envir-
genetic transmission as although these parents and off- onmental transmission is indicated if the parent–offspring
spring are genetically related, the parents do not raise the association is observed only in the exposed offspring.
child and hence have no environmental influence. On the Similarly, the case–control11 design includes matched
other hand, associations between adoptive parents and parent–child control pairs who share the same proportion
offspring suggest environmental transmission as these of genetic and environmental factors as the case
parents and offspring are genetically unrelated, and are parent–child pairs, but do not share the candidate expo-
only connected through the environment. In children-of- sure. As the matching is done by the researchers here, it is
twins studies, children of monozygotic twins are as crucial that the process is thorough so that it can be rea-
genetically similar to their twin aunt/uncle as they are to sonably argued that unmeasured confounders are unlikely
their twin parent, whereas children of dizygotic twins to bias the results. Matched-pairs designs cannot be used to
share less genetic similarity with their aunt/uncle. Higher investigate rGE, as they do not directly measure genetic
monozygotic than dizygotic avuncular correlations effects. However, sibling comparison studies generally rule
(between uncle/aunt and niece/nephew) are likely due to out passive rGE, as the random distribution of parental
the higher proportion of shared genes, suggesting genetic alleles across offspring ensures that siblings are equally
transmission, whereas higher parent–offspring than likely to receive genes associated with the exposure in the
monozygotic or dizygotic avuncular correlation indicates parent, and the outcome in the offspring. Evocative rGE can
environmental transmission through the shared also be ruled out if exposure to the parental characteristic
parent–child environment. Another key characteristic of definitively precedes the offspring outcome.
Fig. 2 Schematic diagrams demonstrating the principles underlying commonly used genetically informative designs which separate
genetic and environmental mechanisms of transmission in parent–offspring associations. A In adoption and related designs, knowledge of
the type of relationship shared between parent and offspring is leveraged to gain insight into genetic and environmental factors underlying parent-
to-offspring associations. Lived-with biological parents can influence offspring through both genetic and environmental transmission, as they provide
both genes and the rearing environment. Not-lived-with biological parents who have no contact with the offspring provide only genes, indicating
genetic transmission, whereas adoptive or step-parents provide only the rearing environment, indicating environmental transmission. In children-of-
twins studies, children of identical (monozygotic) twins are as genetically similar to their aunt/uncle as they are to their parents (50% shared genes),
whereas children of fraternal (dizygotic) twins share 25% of genes with their aunt/uncle. Higher monozygotic than dizygotic avuncular correlations
(between uncle/aunt and niece/nephew, i.e. between Twin 1 and Child 2 or Twin 2 and Child 1) are likely due to a higher proportion of shared genes,
suggesting genetic transmission, whereas higher parent–offspring than avuncular correlation suggests environmental transmission of a parental
factor, above and beyond the effect of shared genetic or environmental effects. B In sibling comparison studies, the association between a specific
parental factor and offspring outcome is studied in exposed versus unexposed offspring, as siblings are naturally matched for parentally provided
genes and a rearing environment. Environmental transmission is indicated if the parent–offspring association is observed only in the exposed
offspring. C In molecular genetics studies, the effect of shared parent–offspring (i.e. transmitted) genes on offspring outcome indicates the presence
of genetic transmission. However, both transmitted genes and non-transmitted parental genes can also have an indirect (i.e. environmentally
mediated) effect on offspring through parental traits that are genetically influenced; this is otherwise known as genetic nurture.
Table 1 Overview of current designs that can be used to study mechanisms of transmission underlying associations between parental characteristics and
offspring outcomes.
Design, Genetic transmission Environmental transmission Gene–environment correlation Advantages Disadvantages
reference
Behavioural genetics designs

Adoption5 Association between a biological parent Adoptee’s relative method: association Higher correlation between biological and - If adoption occurs at birth, passive - Generalisability to the general
and their adopted-away offspring (shared between a parent and their adoptive living-together parents and offspring rGE influences (on factors outside population could be limited, as
genes only) indicates genetic transmission offspring (rearing only) indicates (genes plus rearing) than adoptive parents of the intrauterine environment) adoptees may have a higher risk of
environmental transmission and offspring (rearing only) suggests can be excluded as biological experiencing a suboptimal prenatal
Adoptee study method/siblings-reared- passive rGE parents would have no rearing environment
apart: higher correlation between a Trait correlation between biological parents effect on the offspring - Samples can be difficult to obtain
biological parent and their lived-with and their adopted-away offspring (shared and are usually small
offspring (genes plus rearing) than their genes only) indicates genetic liability, and - Non-random process of adoption
adopted- away offspring (genes only) subsequent adoptee correlation with the may introduce selection bias
indicates environmental transmission environment provided by their adoptive - Increase in open adoption (contact
parent suggests evocative rGE between biological and adoptive
families) confounds the design
Assisted Higher correlation between a genetically Association between a genetically Not studied - Effective for testing short and - Samples can be difficult to obtain
Jami et al. Translational Psychiatry (2021)11:197
conception7 related birth mother (e.g. homologous unrelated birth mother (e.g. egg, oocyte or long-term effects of the prenatal and are usually small
in vitro fertilisation or sperm donation) and embryo donation, surrogacy) and her environment - Generalisability to the general
her offspring (genes plus prenatal offspring (prenatal environment only) population could be limited
environment) than a genetically unrelated indicates environmental transmission - Prenatal behaviours of mothers who
birth mother and her offspring (prenatal use assisted conception may
environment only) indicates genetic introduce selection bias
transmission - Samples are generally very
heterogeneous
- Inclusion of families with a within-
family donation would bias the
design
- Design is not optimal for
investigating gene–environment
correlations
Triparental family Association between an offspring and their Association between an offspring and their Higher offspring correlation with their - Representative of the general - Contact with not-lived-with parents
(offspring- not-lived-with biological parent (genes step-parent (rearing only) indicates lived-with biological parent (genes plus population as all types of can upwardly bias estimate of
focused: multiple only) indicates genetic transmission environmental transmission rearing) than with their step-parent (rearing parent–offspring relationships are genetic influences due to passive rGE
parental only) suggests passive rGE included - Databases with details of family
relationships of Offspring correlation with their not-lived- - Large sample sizes can be attained structure are rare
one offspring)8 with biological parent (shared genes only)
indicates genetic liability, and subsequent
offspring correlation with the environment
provided by their step-parent suggests
evocative rGE
Multiple Association between a parent and their Association between a parent and their Higher parental correlation with their lived- - Representative of the general - Contact with not-lived-with parents
parenting not-lived-with biological offspring (genes step-child (rearing only) indicates with biological children (genes plus population as all types of can upwardly bias estimate of
relationships only) indicates genetic transmission environmental transmission rearing) than with their step-children parent–offspring relationships are genetic influences due to passive rGE
(parent-focused; (rearing only) suggests passive rGE included - Databases with details of family
multiple offspring - Large sample sizes can be attained structure are rare
relationships of - Cannot investigate evocative rGE as
one parent)9 for each child in this design,
information from only one parent
is known
Page 5 of 38
Table 1 continued
reference
Children-of-twins6 Higher monozygotic–avuncular correlation Higher parent–child correlation (genes plus If a parental characteristic is largely - Can determine if the familial - Samples can be difficult to obtain
(between MZ twin uncle/aunt and niece/ rearing) than monozygotic avuncular estimated as heritable (under the effect of correlation is due to genetic or - Assumes that the size of the genetic
nephew; 50% shared genes) than correlations (genes only) indicates genes) in a parent-based twin sample but environmental factors contribution to variation in parent
dizygotic–avuncular correlation (25% environmental transmission is under the influence of the shared - Extended children-of-twins studies and offspring phenotype is the same
shared genes) indicates genetic environment in a child-based twin sample, can incorporate siblings and other - Assumes that the same genes
transmission this suggests passive rGE members of the pedigree and influence the phenotype in both the
Estimation of a parental characteristic as estimate additional parameters parent and offspring generation
heritable (under the influence of genest) in
a child-based twin sample suggests
evocative rGE
Extended twin Not studied, as genetic transmission is not The correlation between parental and Covariance between the additive genetic - Powerful for estimating shared - Cultural transmission can be easily
(twins and their estimated but fixed to 0.5 (50% of genes offspring phenotype indicates cultural (i.e. effect and parental transmission suggests environmental effects of a specific underestimated if assumptions of
parents)122 are passed on from parent to child) in the environmental) transmission - this captures passive rGE parental trait that arise due to the design are violated or the study
model* part of the shared environment effect that cultural transmission or social is underpowered
is explained by parent-to-child transmission homogamy
- Design can be used to study the
impact of other family

relationships, including siblings
- Design can be used to estimate
twin-based heritability
Matched-pairs designs
Sibling Not studied, as the familial resemblance Comparison of outcomes in children with a Not studied - Generally excludes passive rGE as - Requires differential exposure
comparison10 between full siblings could be due to specific parental exposure and their siblings typically share the same between siblings, which can elicit
genetic or environmental factors unexposed full sibling who is otherwise parentally provided environment selection bias
naturally matched for familial (genetic and - Can exclude evocative rGE within - Cannot distinguish if the familial
environmental) risk; higher outcome levels the design if certain that the resemblance between siblings is due
in exposed than unexposed siblings parental exposure precedes to genetic or environmental factors
indicates environmental transmission offspring outcome - Design is not optimal for
investigating gene–environment
correlations
Case–control11 Not studied, as cases and control Parent-offspring pairs are manually Not studied - Representative of the general - Matching is done by the researcher
parent–offspring pairs are matched on matched on familial and genetic risk. population and is susceptible to errors
genetic risk Outcomes are compared between children - If matched well, ensures no effect - Resources required to find matched
with a specific parental exposure (cases) of confounding factors parent–offspring pairs
and unexposed children (controls); higher - Cannot investigate genetic
outcome levels in cases than controls transmission or gene–environment
indicates environmental transmission correlation
Molecular genetics designs
Within-family PGS: The disappearance of an observed The remaining parent–offspring correlation, Reduction of parent–offspring correlation - Can test whether parent–offspring - PGS capture only a small proportion
genetic sensitivity parent–offspring correlation after adjusting after adjusting for offspring PGS for the after adjusting for offspring PGS suggests associations are partly due to of heritability and cannot index the
analysis13 for offspring PGS for the predictor and predictor and outcome traits, estimates passive rGE shared genes effect of all shared genes
outcome traits indicates genetic environmental transmission - Requires well-powered GWAS
transmission summary statistics
Within-family PGS: Association between PGS based on Transmitted/non-transmitted method: Association between offspring PGS and - Can examine environmental - Requires well-powered GWAS
genetic transmitted parental genes and offspring association between PGS based on non- parenting suggests passive rGE transmission without parental summary statistics
nurture14,83 outcome indicates genetic transmission transmitted parental genes and offspring Association of offspring PGS with phenotypic information - Datasets with parent–offspring
outcome indicates genetic nurture parenting, after adjusting for parental PGS genotyped duos or trios are rare
Statistical control method: association suggests evocative rGE
between parental PGS and offspring
outcome, after adjusting for offspring PGS
Page 6 of 38
Table 1 continued
reference
to account for shared parent–child genetic

effects indicates genetic nurture
Maternal-effects Not studied* The estimated effect of maternal or Covariance between direct genetic effect - Can estimate the overall impact of - Cannot model both maternal and
genome-wide paternal genetic nurture: variance in and genetic nurturing effect suggests genetic nurture from mother or paternal genetic nurture effects at
complex trait offspring outcome that is explained by the passive rGE father the same time
analysis (M- effect of maternal or paternal genotype - Representative of the general - Large sample sizes are required to
GCTA)16 (after accounting for transmitted genetic population estimate multiple variance
effects) - Design can be used to estimate components based on genetic data
SNP-based heritability - Datasets with parent–offspring
genotyped duos or trios are rare
Relatedness Not studied* The overall estimated effect of parental Covariance between direct genetic effect - Can estimate the overall impact of - Assumes that maternal and paternal
disequilibrium genetic nurture: variance in offspring and genetic nurturing effect suggests genetic nurture from both parents genetic effects are the same and of
regression87 outcome that is explained by the effect of passive rGE combined equal magnitude
mid-parent genotype (after accounting for - Representative of the general - Large sample sizes are required to
transmitted genetic effects) population estimate multiple variance
- Design can be used to estimate components based on genetic data
SNP-based heritability - Datasets with parent–offspring

genotyped trios are rare
Trio-GCTA18 Not studied* The Eestimated effect of maternal and Covariance between direct genetic effect - Can estimate the individual impact - Large sample sizes are required to
paternal genetic nurture: variance in and genetic nurturing effect suggests of genetic nurture from both estimate multiple variance
offspring outcome that is separately passive rGE parents in the same model components based on genetic data
explained by the indirect effect of maternal - Representative of the general - Datasets with parent–offspring
and paternal genotype (after accounting population genotyped duos or trios are rare
for transmitted genetic effects) - Design can be used to estimate
SNP-based heritability
rGE gene–environment correlation, PGS polygenic scores, SNP-based heritability variance in a target trait that is explained by the additive genetic effect of common genetic variants known as single-nucleotide
polymorphisms.
*These designs can be used to estimate twin or SNP-based heritability for offspring outcomes, i.e. the proportion of variance in a phenotype that can be explained by genetic variation in the population under study. This
does not directly index genetic transmission, although it is implicitly known that children receive their genes from their parents.
Page 7 of 38
Molecular genetics designs only a part of the overall parent-to-child environmental

Recent advances in molecular genetics provide novel transmission. Parental traits that are not under the
ways of investigating genetic and environment effects influence of common genetic variation may also influence
underlying parent–offspring associations by using geno- offspring outcomes. To test whether specific parental
mic data. In molecular genetics studies, the effect of behaviours are responsible for observed genetic nurturing
genetic variants transmitted from parent-to-offspring on effects, the parental phenotype can be included as a
offspring behaviour indicates the presence of genetic covariate in within-family genetic nurture analyses, M-
transmission. As described in Figs. 1 and 2, parental genes GCTA, RDR or trio-GCTA. If a genetic nurturing effect
can also have an indirect effect on offspring, through on offspring behaviour is attenuated with the inclusion of
parental traits that are environmentally mediated but the parental phenotype to the model, the parental phe-
genetically influenced; a process otherwise known as notype is shown to be involved in the manifestation of the
genetic nurture. One way to separate genetic transmission genetic nurturing effect. As with behavioural genetics
and genetic nurture effects underlying specific designs, molecular genetics designs can be used to
parent–offspring associations is the use of polygenic investigate rGE, by estimating covariance between addi-
scores. Polygenic scores (PGS) represent an aggregate tive genetic effects and indirect genetic nurturing effects
genetic liability for a trait, determined by the presence and (Table 1).
effect sizes of alleles associated with the trait12. In within-
family PGS genetic sensitivity analysis, offspring PGS for Methods
exposure and outcome traits are included as covariates in We searched for articles investigating associations
the regression analyses to explore whether the association between parental characteristics and offspring mental
between a parental exposure variable and offspring outcome health and related outcomes. We defined related traits as
is attenuated by the offspring’s PGS. If that is the case, those that have an established link to mental health in the
genetic transmission explains part of the parent–offspring literature. The Web of Science database was used to
association13. Although adjusting for PGS does not entirely conduct a systematic search of studies published from
eliminate genetic transmission as current PGS capture only 2014 to June 2020. The search terms consisted of study
a small proportion of trait heritability, such sensitivity ana- design variables (“children-of-twins” or “offspring of
lyses can show whether shared genes partially account for twins” or “adoption” or “assisted conception” or “sibling
an observed parent–offspring association. In within-family comparison” or “genetic nurture” or “non-transmitted” or
PGS genetic nurture analyses, PGS can additionally be used “polygenic score”), parent variables (“parent” or “mother”
to estimate the environmental influence of parental alleles or “father” or “maternal*” or “paternal*”), offspring vari-
not passed on to the offspring14,15. If PGS based on non- ables (“offspring” or “child*”) and topic variables (“gene*”
transmitted parental alleles are associated with an offspring or “environment”). The search did not include predictor
trait (transmitted/non-transmitted method in Table 1), the or outcome-specific search terms, so as not to limit the
effect of these parental genes on offspring behaviour likely review to a particular set of traits. We restricted the
occurs via an environment pathway, i.e. genetic nurture. search to scientific articles published in English. Through
Similarly, if parental PGS are associated with an offspring the results of the initial search, we identified additional
trait, after adjusting for the child’s own PGS (statistical designs that were relevant (Table 1), and ran separate
control method in Table 1), this also suggests a nurturing follow-up searches for these study design variables
effect of parental genes beyond that which is due to trans- (“extended twin” or “triparental” or “multiple parenting
mitted genes (see statistical control method in Table 1). The relationships design” or “matched pair” or “genome-wide
overall contribution of genetic nurture to offspring traits can complex trait analyses” or “relatedness disequilibrium
be estimated using maternal-effects genome complex trait regression”). Aside from the database searches, we scan-
analysis (M-GCTA)16, relatedness disequilibrium regression ned the references of papers for relevant studies and
(RDR)17 or trio-GCTA18 (Table 1). Each of these methods checked bioRxiv and medRxiv for relevant preprints.
uses genotyped data from unrelated parent–offspring pairs After removing duplicates, the overall search yielded
to estimate the variance in offspring behaviour that is 2097 hits. Studies were included in the systematic
explained by their own genotype (SNP-based heritability; review when the following criteria were met: the asso-
heritability accounted for by differences in measured genetic ciation between a parental characteristic and offspring
variants known as single-nucleotide polymorphisms) and behaviour was examined, a genetically informative
genetic nurture (parental additive genetic effects acting via design was used, and the phenotype in the offspring was
genetically influenced parental behaviours). a mental health or related trait. As current literature
It is important to note that as current genetic nurture shows that most complex traits have a polygenic
designs only index parental effects that are captured by architecture, candidate gene studies were excluded
their common genetic variation, these designs capture from this review.
Results Offspring internalising behaviours

After screening and assessment of search results Intergenerational transmission of internalising behaviours
(Fig. 3), we identified 89 articles for inclusion in this Studies investigating the association between parent and
review. We present our synthesis of the literature by offspring internalising behaviours (Table 3), including
grouping the studies according to the offspring outcome depression and anxiety, showed substantial evidence of
in the following sections: internalising behaviours, genetic transmission of depressive symptoms19–22, and
externalising behaviours, educational attainment, sub- major depressive disorder (MDD) diagnosis23. This is in
stance use and personality. The number of studies line with twin literature which shows that depression is a
and key findings for each outcome are summarised in heritable phenotype3. After accounting for genetic effects,
Table 2. Details of all studies and their results are parental depression was associated with offspring inter-
reported in Tables 3–7. Effect sizes showing the relative nalising behaviours through environmental pathways, and
contribution of genetic and environmental factors in these associations were observed throughout child-
parent–offspring associations are included in the tables hood20,21,24,25, adolescence19,26, and adulthood23. Simi-
when studies provided standardised, well-interpretable larly, associations between parental anxiety and offspring
statistics, i.e., odds ratios, percentage of variance internalising behaviours also showed evidence of envir-
explained or standardised betas. onmental transmission across development, from
Fig. 3 Flow chart of study selection. A description of the screening and assessment procedure, reporting the number of records excluded and
reasons for exclusion at each stage.
Table 2 Summary of findings from the reviewed studies.
Trait(s) Number of Designs Genetic overlap Environmental transmission Gene–environment correlation
studies
Offspring internalising behaviours

Parental internalising 19 11 adoption studies19,20,25–28,30,32,36,41,57 There was evidence of genetic overlap There was evidence that parental anxiety No evidence of evocative rGE was
behaviours Five children-of-twins studies19,21,22,29,123 between parental depression and offspring and depression were associated with found, but child-to-parent effects
Three sibling comparison studies24,31,34 internalising symptoms, but not parental offspring internalising symptoms through were identified
One multiple parenting relationships anxiety environmental pathways
study23
Parenting 8 Four children-of-twins studies37–40 There was no evidence of genetic overlap There was evidence that negative No evidence of evocative rGE was
Two sibling comparison studies42,65 between parenting factors and offspring parenting behaviours were associated with found, but child-to-parent effects
Two adoption studies36,41 internalising behaviours more offspring internalising behaviours, were identified
and positive parenting was associated with
fewer offspring internalising behaviours
Genetic nurture 2 One M-GCTA study43 Not studied There was evidence of a genetic nurturing One study reported a negative rGE
One RDR study44 effect on offspring depressive (but not between genetic nurture and
anxiety) symptoms offspring depressive symptoms
Parental educational 1 One children-of-twins and siblings study45 There was evidence of genetic overlap Parental educational attainment was not Not studied
attainment between parental educational attainment and associated with offspring depression
offspring depressive symptoms through an environmental pathway
Parental substance use 1 One sibling comparison study47 Not studied Maternal drinking during pregnancy was Not studied
associated with emotional reactivity and
somatic complaints, but associations with
anxiety and depressive symptoms were
confounded
Offspring externalising symptoms
Parental externalising 9 Seven adoption studies48–54 There was evidence of genetic transmission of There was evidence that parent and Not studied
behaviours One multiple parenting relationships criminal behaviours; evidence for other offspring criminal behaviours were
study55 externalising symptoms was ambiguous, associated with environmental pathways
One triparental study8 although better-powered studies tended to
find supportive evidence
Parental internalising 11 Six adoption studies19,20,25,41,51,57 There was evidence of genetic overlap There was evidence that parental One study reported evocative rGE
behaviours Three children-of-twins studies19,22,56 between parental depression and offspring depression was associated with offspring effects on the association
Three sibling comparison studies21,24,31 externalising symptoms internalising symptoms through between parental depression and
environmental pathways offspring externalising symptoms
Parenting 14 11 adoption studies41,48–53,57,60,61,64 There was some evidence of genetic overlap There was evidence that negative There was some evidence of
Two sibling comparison studies62,65 between parenting factors and offspring parenting behaviours were associated with evocative rGE and other child-to-
One children-of-twins study59 externalising behaviours more offspring externalising behaviours, parent effects
whereas positive parenting was associated
with fewer offspring externalising
behaviours
Parental substance use 10 Seven sibling comparison studies47,67,70–74 There was evidence of genetic overlap There was mixed evidence for an Not studied
Three adoption studies51,64,66 between parental drug abuse and smoking and environmental association between
One children-of-twins study67 offspring externalising behaviours parental substance use and offspring
externalising behaviours
Parental education 3 One within-family PGS genetic sensitivity There was evidence of genetic overlap There was some evidence of Not studied
study13 between parental educational attainment and environmental associations between
One within-family PGS genetic nurture offspring externalising symptoms maternal education and offspring
study75 attention-deficit hyperactivity
One children-of-twins study45 disorder (ADHD)
Genetic nurture 1 One within-family PGS study75 Not studied No genetic nurturing effect on offspring Not studied
ADHD was observed
Page 10 of 38
Table 2 continued
Trait(s) Number of Designs Genetic overlap Environmental transmission Gene–environment correlation
studies
Offspring educational attainment

Parental educational 9 Four adoption studies80,81,90,124 There was substantial evidence of genetic There was evidence that parent and One study reported passive rGE
attainment Three within-family PGS genetic sensitivity overlap between parental and offspring offspring educational attainment were effects underlying the association
studies13,82,84 educational attainment associated through environmental between parent and offspring
One extended twin study79 pathways educational attainment
One children-of-twins and siblings study45
Genetic nurture 12 11 within-family PGS Not studied There was evidence of a genetic nurturing There was evidence of passive rGE
studies14,15,75,78,82–86,88,89 effect on offspring educational attainment on offspring educational
One RDR study17 attainment
Maternal smoking 2 Two sibling comparison studies67,71 There was evidence of genetic overlap There was little evidence of environmental Not studied
during pregnancy One children-of-twins study67 between maternal smoking during pregnancy associations between maternal smoking
and offspring cognition during pregnancy and offspring cognition
Offspring substance use
Parental substance use 15 Four children-of-twin studies67,94,96,100 There was evidence of genetic overlap There was evidence of environmental One study reported passive rGE
behaviours Two adoption studies95,101 between parental and offspring substance use associations between parental and underlying the association
Two sibling comparison studies67,105 behaviours offspring substance use behaviours between parent and offspring
Two triparental studies8,98 substance use behaviours
Two multiple parenting relationships
studies9,99
Two extended-family designs42,97
One within-family PGS genetic sensitivity
analysis study100
One extended twin study103
One matched-pair case–control study11
Parenting 4 Three adoption studies104,107,108 Not studied There was evidence of protective effects of Not studied
One sibling comparison study109 several parental factors on offspring
substance use behaviours
Offspring personality
Parental characteristics 6 Three adoption studies61,110,111 There was some evidence of genetic overlap There was some evidence of There was evidence of evocative
One sibling comparison study71 between parental characteristics and offspring environmental associations between rGE underlying associations
One children-of-twins study29 personality parental and offspring personality between parenting behaviours
One extended twin study112 and offspring social behaviours
rGE gene–environment correlation, M-GCTA maternal-effects genome-wide complex traits analysis, RDR relatedness disequilibrium regression, PGS polygenic scores.
Page 11 of 38
Table 3 Detailed characteristics of studies investigating offspring internalising behaviours (N = 30).
Study Design Sample Parental attribute Child attribute Control variables Genetic overlap Environmental G–E interplay
(predictor) (outcome) transmission
Brooker et al.27 Adoption EGDS Adoptive & birth parent Internalising problems: No, birth parent Yes, adoptive parent G × E: high birth parent
361 families anxiety maternal and paternal anxiety did not anxiety predicted anxiety × greater
Offspring age: : self-report, BAI report, composite predict offspring offspring internalising attention control × low
18–27 months score, CBCL internalising problems (β = 0.25) adoptive parent
problems anxiety: fewer
internalising problems
Brooker et al.28 Adoption EGDS Adoptive parent anxiety: Negative affect: Prenatal risk and obstetric No, birth parent Yes, adoptive parent No evidence of
349 families self-report, BAI observation and complications, adoption negative affect did anxiety predicted evocative rGE, but
Age: 9–27 months Birth parent negative adoptive-parent report, openness not predict offspring negative child-to-parent
affect: self-report, ATQ composite score, ICQ offspring negative effect (effect size effects found
and TBAQ effect (effect size not clear)
not clear)
Marceau et al.41 Adoption EGDS Over-reactive parenting: Internalising behaviours: Adoption openness No, birth mother Yes, paternal (but not
361 families self-report, PS parent report, CBCL risk did not predict maternal) over-reactive
Age: 9 months 6 years Birth mother risk: self- offspring parenting predicted
report, composite score, internalising offspring internalising
substance use, depression behaviours (effect behaviours (effect size
(BDI) & anxiety (BAI) size not clear) not clear)
McAdams Adoption, Children-of- Adoption: EGDS Adoptive & parent Internalising problems Adoption sample: Adoption: birth Adoption: no, adoptive No evidence of
et al.19 twins 361 families depression: self-report, BDI (adoption sample): obstetric complications, mother depressive parent depression did evocative rGE, but
Age: 4.5–7 years Depressive symptoms parent report, CBCL adoption openness symptoms not predict subsequent child-to-parent
CoT: TOSS (CoT): self-report, CES-D Internalising problems CoT sample: twin sex, age predicted offspring internalising effects found
287 monozygotic (MZ) & (CoT sample): mother, internalising problems
489 dizygotic (DZ) twin father and self- problems at age 7 CoT: after accounting
families report, CBCL (β = 0.15), but not for genetic relatedness,
Age: 11–22 years age 4.5 or age 6 parental depression
CoT: no shared was associated with
genetic effects offspring internalising
between parental problems (effect size
depression and not clear)
offspring
internalising
problems
Eley et al.29 Children-of-twins TOSS Anxious personality: self- Anxiety: mother, father Twin sex, age No shared genetic Yes, after accounting
387 MZ, 489 DZ families report, KSP and self-report, CBCL effects between for genetic relatedness,
Age: 11–22 years parental anxious parental anxiety was
personality and associated with
offspring anxiety offspring anxiety
symptoms (effect size
not clear)
Roos et al.57 Adoption EGDS Adoptive & birth mother Internalising-only Child sex, child age, Birth mother Adoptive parent G × E: adoptive mother
293 families internalising symptoms: problems: parent adoption openness, internalising internalising symptoms high internalising
Age: 6–7 years self-report, composite report, CBCL obstetric complications symptoms and predicted internalising- symptoms × inherited
score, BAI and BDI Co-occurring internalising processing speed only symptoms (OR = risk of slow processing
Adoptive mother and externalising did not predict 1.17), but not co- speed: co-occurring
uninvolved parenting: self- problems: parent internalising-only occurring symptoms, symptoms
report, APQ report, CBCL symptoms, but uninvolved parenting
Adoptive & birth mother processing speed predicted co-occurring
processing speed: Stroop was associated symptoms (OR = 7.91),
colour-word naming task with co-occurring but not internalising-
symptoms only symptoms and
(OR = 1.88) adoptive parent
processing speed and
Page 12 of 38
offspring outcomes
were unrelated
Table 3 continued
Grabow et al.20 Adoption EPoCH Maternal trauma Internalising behaviours: EPoCH: Timing of Yes, birth mother Adopted mother
541 adoptive frequency: repeated self- parent report, CBCL maternal trauma, depression depression predicted
mother–child dyads, 126 report, mean score, NLES socioeconomic status predicted adopted- offspring internalising
biological Adoptive & birth mother (SES), sex away offspring behaviours (β = 0.15),
mother–child dyads depressive symptoms: self- EGDS: Perinatal risk, internalising and mediated the
Age: 7 years report, BDI adoption openness, behaviours (β = relationship between
SES, sex 0.16) maternal trauma and
offspring internalising
behaviours
Gjerde et al.24 Sibling comparison MoBa Maternal depression: self- Internalising problems: Maternal parity, maternal Not studied Children exposed to
17,830 siblings, 11,599 report, SCL maternal report, CBCL education, child age and concurrent maternal
families child sex depression had more
Age: 6 months to 5 years internalising symptoms
than their unexposed
siblings, but perinatal

maternal symptoms
had no effect
Bekkhus et al.34 Sibling comparison MoBa Maternal anxiety during Infant difficulties: Maternal substance use Not studied No difference in infant
21,980 families with at pregnancy: self-report, SCL maternal report, ICQ during pregnancy, post- difficulties or emotional
least two siblings (short version) Emotional difficulties: birth anxiety, partner difficulties between
Age: 6 months to 3 years maternal report, CBCL disharmony, somatic exposed and
disease, marital status, unexposed siblings
education, age, parity,
child gestational age,
birth complications, sex,
birthweight
Bridgett et al.36 Adoption EGDS Harsh negative parenting: Self-regulation: parent Obstetric and neonatal Yes, birth mother Yes, adoptive parent No evocative rGE, but
361 families observation report (Children’s complications, adoption self-regulation harsh parenting child-to-parent effects
Age: 4.5–6 years Biological parent self- Behaviour openness, child anger predicted adopted- predicted poor of child anger found
regulation: Go/no Go task Questionnaire) and Go/ (parent report), gender away offspring’s offspring self-regulation
computerised task no Go self-regulation (β = (β = −0.22 to −0.25)
computerised task 0.23)
Hannigan et al.21 Multiple children-of- MoBa Maternal depressive Internalising problems: Prenatal depression: Yes, there were Yes, after accounting
twins and siblings 22,195 mothers, 25,299 symptoms: self-report, SCL maternal report, CBCL adjusted for concurrent shared genetic for genetic relatedness
children depression effects between and prenatal
Age: 18–60 months maternal depression, concurrent
depression and maternal depression
offspring was associated with
internalising offspring internalising
problems effect problems (effect size
size not clear) not clear)
Liskola et al.26 Adoption FAS Depressive symptoms: self- Depressive symptoms: Child age, gender, age at Not studied Adoptive paternal (but
548 international adopted report, GHQ self-report, CDI adoption, type of not maternal)
children placement before depressive symptoms
Age: 9–12 years adoption, the continent were associated with
of birth, adoptive offspring depressive
family SES symptoms
Page 13 of 38
Table 3 continued
Kendler et al.23 Multiple parenting Snr Major depression: Major depression: None Yes, MD status of Yes, MD status of No G × E
relationships design 2,041,816 intact, 14,104 diagnosis, hospital diagnosis, hospital not-lived-with adoptive or step- interaction found
adoptive, 115,501 not- discharge and outpatient discharge and biological parents parents was associated
lived-with father, care registers outpatient care registers was associated with offspring MD (r =
57,826 stepfather, 29,205 with offspring MD 0.08)
triparental families (r = 0.08)
Age: 26–56 years
Ahmadzadeh Adoption EGDS Adoptive parent anxiety: Anxiety: maternal and The weighted risk score No, birth parents’ Adoptive paternal No evocative rGE, but
et al.30 305 families self-report, ST-AIA paternal report, CBCL of obstetric internalising anxiety (but not child-to-mother
Age: 6–8 years Birth parents’ internalising complications, adoption problems did not maternal) predicted effects found
problems: mother & father openness, child sex predict adopted- offspring anxiety (β =
self-report, composite away offspring 0.10)
score, CIDI and FH-RDC anxiety
Gjerde et al.22 Multiple children-of- MoBa Concurrent maternal Emotional problems: Child sex, maternal age Yes, there were Yes, after accounting
twins and siblings 22,316 mothers and depression symptoms: self- maternal report, CBCL shared genetic for genetic relatedness,
35,589 offspring report, SCL effects between maternal depression
Age: 1.5–5 years maternal was associated with
depression and offspring internalising
offspring emotional problems (R2 =
problems (R2 = 0.3–2.2%)
21.1–28.5%)
Hails et al.25 Adoption EGDS Adoptive parent Internalising symptoms: Adoption openness, No, birth mother Adoptive paternal (but
561 families depression: self-report, parent and teacher prenatal risk and internalising not maternal)
Age: 9 months to 6 years BDI-IIBirth report, CBCL and (TRF obstetric complications, symptoms did not depression predicted
mother internalising infant negative predict offspring parent-reported (but
symptoms: self-report, CIDI emotionality internalising not teacher-reported)
symptoms offspring internalising
symptoms (β = 0.21)
Field et al.32 Adoption EGDS Adoptive and birth parent Anxiety symptoms: No, birth parent Adoptive maternal and No evidence of
561 families anxiety: self-report, parent report, an anxiety did not paternal anxiety equally evocative rGE found
Age: 18 months to composite score of two average of the maternal predict offspring predicted both
4.5 years measurements, BAI and paternal anxiety symptoms offspring anxiety
report, CBCL symptoms and change
in anxiety symptoms
(effect size not clear)
Gjerde et al.31 Sibling comparison MoBa Maternal anxiety: self- Child internalising Child age, child sex, Not studied Children exposed to
11,553 mothers and report, SCL problems: maternal maternal depressive concurrent maternal
17,724 children report, CBCL symptoms, parity, anxiety had more
Age: 1.5–5 years education internalising symptoms
than their unexposed
siblings, but perinatal
maternal symptoms
had no effect
O’Reilly et al.123 Children of siblings Snr Suicidal behaviour: suicide Suicidal behaviour: Offspring: parity. Parental: Yes, there were Yes, after accounting
2,762,883 unique offspring attempt or death by suicide attempt or death age at birth, educational shared genetic for genetic relatedness,
Age: 12 and over suicide, National Patient by suicide, National attainment, Swedish by effects between parental suicidal
Register and Cause of Patient Register and birth, mental illness, parental and behaviour was
Death register, prior to Cause of Death register criminal convictions offspring suicidal associated with
offspring age 18 offspring suicidal
Page 14 of 38
Table 3 continued
behaviour (effect behaviour effect size

size not clear) not clear)
37
Horwitz et al. Extended children-of- TOSS, TCHAD Parental criticism: self- Somatic symptoms: Age, sex, age difference No shared genetic Yes, after accounting No evidence of passive
twins 858 twin families, 690 twin report, EES parent and self-report, for the cousin offspring effects between for genetic relatedness, or evocative rGE found
families composite score, CBCL in TOSS parental criticism parental criticism was
Age: 11–22 years, and offspring associated with
16–17 years somatic symptoms offspring somatic
symptoms (effect size
not clear)
Guimond et al.65 Sibling comparison QNTS Perceived maternal support Depressive symptoms: Genetically-controlled Not studied No, perceived maternal No evidence of
164 twin pairs and negativity: child self-report, CDI analyses using MZ twin- support and negativity evocative rGE, but
Age: 13–14 years report, NRI difference score were not associated child-to-parent
with offspring effects found
depressive symptoms
McAdams Children-of-twins TOSS Expressed affection and Self-worth: self- Twin sex and age No shared genetic Yes, after accounting
et al.38 387 MZ, 489 DZ families closeness with child: self- report, HPCS effects between for genetic relatedness,
Age: 11–22 years report expressed affection expressed affection and
or closeness with closeness with the child
child and offspring were associated with
self-worth offspring self-worth
Hannigan et al.39 Children-of-twins TOSS Relationship quality with Internalising problems: No shared genetic Yes, after accounting
909 twin pairs offspring: maternal and self-report, CBCL effects between for genetic relatedness,
Age: 11–22 years paternal report, P-CAS, parental parental relationship
EAS and P-CRQ relationship quality quality with offspring
with offspring, and was associated with
offspring offspring internalising
internalising problems (effect size
problems not clear)
Ahmadzadeh Extended children-of- TOSS, TCHAD Parental criticism: self- Internalising symptoms: Child age, sex No shared genetic Yes, after accounting
et al.40 twins 876 twin families, 1030 report, EES parent and self-report, effects between for genetic relatedness,
twin families composite score, CBCL parental criticism parental criticism was
Age: 11–22 years and YSR and offspring associated with
internalising offspring internalising
symptoms symptoms (effect size
not clear)
Kendler et al.42 Sibling comparison Snr Adoptive parenting: Major depression: Parental age at birth, Not studied Children exposed to
666 full sibships and 2596 protective effect of high- diagnosis, hospital high-risk status of the adoptive parenting had
half-sibships of high-risk quality rearing discharge, outpatient other parent of a half- a lower risk of MDD
(MDD diagnosis) environment care registers, primary sibling, child sex than their unexposed
biological parents care registry siblings, this protective
Age: 15 and over effect disappeared
when the adoptive
family was disrupted or
if there was a high-risk
adoptive parent
Jami et al.43 M-GCTA, children-of- MoBa Genetic nurture: M-GCTA, Anxiety symptoms: Sex, genotyping batch, Not studied After accounting for No evidence of
twins and siblings M-GCTA: 3801 maternal and paternal maternal report, SCARED first ten principal shared genetic effects, rGE found
parent–offspring trios, genotypes Depressive symptoms: components maternal or paternal
extended CoT: 10,688 Shared maternal or maternal report, SMFQ genes did not explain
children paternal environment: significant variance in
Age: 8 years offspring depression or
Page 15 of 38
Table 3 continued
children-of-twins and anxiety symptoms, and

siblings there were no shared
maternal or paternal
environment effects
Cheesman Relatedness MoBa Genetic nurture: RDR, mid- Anxiety symptoms: Child sex. RDR: ten Not studied After accounting for Negative rGE between
et al.44 disequilibrium regression RDR: 11,598 parent genotype maternal report, SCARED principal components shared genetic effects, genetic nurture and
(RDR), children-of-twins parent–offspring trios, Maternal emotional Depressive symptoms: and genotyping batch parental genes offspring depressive
and siblings extended CoT: 26,086 symptoms: self-report, maternal report, SMFQ explained significant symptoms
pairs of relatives common factor score of 5 variance in offspring
Age: 8 years measurements, SCL-8 depression (but not
Shared parental anxiety) symptoms, this
environment: children-of- effect was partly
twins and siblings mediated by maternal
emotional symptoms
Shared parental
environmental effect
was observed for
offspring depression
(but not anxiety)
symptoms
Lund et al.47 Sibling comparison MoBa Maternal alcohol Emotional problems: Parity, unplanned Not studied Exposed children were
14,639 mothers, 25,744 consumption during maternal report, CBCL pregnancy, daily more emotionally
children pregnancy: self-report, Emotional reactivity smoking, pre-pregnancy reactive and had more
Age: 1.5–5 years AUDIT-C Anxious/depressed abstinence from alcohol somatic complaints, but
Somatic complaints did not have more
anxious depressive
symptoms, than their
unexposed siblings
Torvik et al.45 Children-of-twins and MoBa Educational attainment Depression symptoms: Yes, there were No, after accounting for
siblings 34,958 children (EA): self-report, highest maternal report, SMFQ shared genetic genetic relatedness,
Age: 8 years level completed effects between parental EA was not
parental EA and associated with
offspring offspring depression
depression
symptoms (effect
size not clear)
G–E gene–environment, G × E gene–environment interaction, rGE gene–environment correlation.

Design = M-GCTA maternal-effects genome-wide complex traits analysis.
Samples = EGDS Early Growth and Development Study, EPoCH Early Parenting of Children study, FAS Finnish Adoption Study, MoBa Norwegian Mother Father and Child Study, QNTC Quebec Newborn Twin Study, Snr
Swedish national registers, TCHAD Twin Study of Child and Adolescent Development, TOSS Twin Offspring Study of Sweden.
Measures = APQ Alabama Parenting Questionnaire, ATQ Adult Temperament Questionnaire, AUDIT-C Alcohol Use Disorder Identification Test-Consumption, BAI Beck Anxiety Inventory, BDI Beck Depression Inventory, CBCL
Child Behaviour Checklist, CDI Children’s Depression Inventory, CES-D Centre for Epidemiological Studies Depression Scale, CIDI Composite International Diagnostic Instrument, EAS Expression of Affection Scale, EES
Expression Emotion Scale, FH-RDC Family History-Research Diagnostic Criteria, GHQ General Health Questionnaire, HPCS Harter Perceived Competence Scale, ICQ Infant Characteristics Questionnaire, KSP Karolinska Scales of
Personality, NLES Negative Life Events Scale, NRI Network of Relationships Inventory, P-CAS Parent–Child Agreement Scale, P-CRQ Parent–Child Relationship Questionnaire, PS the Parenting Scale, SCARED Screen for Child
Anxiety Related Disorders, SCL Symptoms Checklist, SMFQ Short Mood and Feelings Questionnaire, S-TAIA State-Trait Anxiety Inventory for Adults, TBAQ Toddler Behaviour Assessment Questionnaire, TRF Teacher Report
Form, YSR Youth Self Reports.
Statistics = β standardised parameter estimate, OR odds ratio, R2 percentage of variance explained, r weighted tetrachoric correlation. Effect sizes are not reported for studies that did not investigate both genetic and
environmental transmission.
Page 16 of 38
toddlerhood to early adulthood27–32. However, unlike Negative parenting behaviours, including over-reactive
depression, this association was not partly explained by parenting41, harsh parenting36 and parental criticism37,40
shared genes, as there was no evidence of genetic overlap were associated with more offspring internalising beha-
between parental anxiety and offspring internalising viours, whereas parental expressed affection and a good
behaviours27,29,30,32. The lack of evidence for genetic parent–child relationship quality were associated with
transmission of anxiety is at odds with findings from twin positive offspring self-worth38, and fewer internalising
literature which estimate that 40% of individual differ- problems39, respectively. Of note, an innovative sibling
ences in anxiety are explained by genetic factors3. How- comparison based on Swedish registry data identified a
ever, there are some possible explanations of why genetic protective effect of adoptive parenting in children of high-
transmission is not evident within the adoption and risk biological parents with MDD diagnosis42. In inter-
children-of-twins studies reviewed here. Measures of preting associations between parenting behaviours and
inherited risk in the adoption studies could lack validity, offspring outcomes, it is important to again note that
and may not adequately capture the genetic risk of anxiety these parent–offspring associations can be bidirectional,
from birth parents. Alternatively, as longitudinal studies with each affecting the other over time. Furthermore,
show that genetic factors involved in anxiety change parenting behaviours can be evoked by the offspring’s
across the lifespan33, different genes could be relevant for genetically influenced internalising behaviours. However,
the occurrence of anxiety in early life and adulthood. three adoption studies found no evocative rGE effects of
Therefore, parental anxiety and offspring internalising offspring internalising symptoms32,36,37, although one
symptoms may share fewer common genetic factors that study reported child-to-parent effects wherein child anger
are not easily captured using adoption or children-of- predicted prospective harsh negative parenting36.
twins designs. Even if different genes are involved in
childhood internalising symptoms and adult anxiety, the Genetic nurture
observed environmental association indicates that expo- Genetic nurture is a relatively new topic within psy-
sure to an anxious parent is a risk factor for offspring chiatric genetics, and as such, we identified only two
internalising symptoms. studies that investigated environmentally mediated effects
Overall, environmental associations between parental of parental genes on offspring internalising behaviours
factors and offspring internalising behaviours were gen- (Table 3). Both studies were based on the Norwegian
erally driven by exposure to concurrent parental anxiety Mother, Father and Child (MoBa) sample and estimated
or depression, whereas prenatal and post-natal symptoms variance in offspring depression and anxiety symptoms
did not have a long-lasting effect21,24,31,34. This finding that was explained by indirect parental genetic effects,
stands in contrast to the substantial body of literature that over and above the transmission of genes from parent to
interprets associations between perinatal maternal dis- child. The earlier study, with a smaller sample size, found
tress and offspring mental health outcomes in causal no evidence for genetic nurture43, whereas the subsequent
terms35. Based on the current findings, such study with three times the sample size identified a genetic
parent–offspring associations detected in previous nurturing effect on offspring depressive symptoms that
observational studies are likely to be attributable to was mediated by maternal emotional symptoms44. This
unmeasured rGE, or concurrent parental depression. In finding is in line with the studies reviewed above which
investigating the presence of gene–environment correla- showed environmental associations between maternal
tion, several adoption studies found no evidence of evo- depression and offspring internalising behaviours20,21,24
cative rGE, although some child-to-parent effects were and shows that seemingly environmental associations
identified19,28,30,32,36. These studies highlight the dynamic between parental factors and offspring outcomes may
nature of parent and offspring relationships, where asso- nonetheless be driven by genetically influenced parental
ciations can be bidirectional, with both parent and off- traits.
spring behaviour influencing the other.
Parental educational attainment
Parenting behaviours A large children-of-twins and siblings study investigat-
Children-of-twin studies examining genetic overlap ing associations between parental educational attainment
between parenting and offspring mental health found that and offspring depressive symptoms found evidence of
genes involved in parenting behaviours (such as parental genetic, but not environmental transmission45 (Table 3).
criticism, parental affection and parent–child relationship Genetic overlap between education attainment and
quality) did not overlap with genes involved in offspring depression has been reported previously46, and this study
internalising behaviours37–40 (Table 3). After accounting highlights that without the use of genetically informative
for genetic relatedness, several parenting behaviours were designs to account for genetic transmission, phenotypic
associated with offspring internalising behaviours. associations between parental educational attainment and
offspring internalising symptoms could be misinterpreted in families where the same parent provided both the genes
as causal. and the rearing environment8,55.
Parental anxiety or depression

Parental substance use Evidence from adoption and children-of-twins studies
A large sibling comparison study investigated associa- showed genetic overlap between parental depression and
tions between maternal alcohol use during pregnancy and offspring externalising behaviours, including ADHD19–22,56
offspring emotional problems47 (Table 3). Although (Table 4), whereas associations between overall parental
exposed children were more emotionally reactive and had internalising symptoms and offspring externalising symp-
more somatic complaints than their unexposed siblings, toms showed mixed results in four adoption stu-
associations between maternal drinking and offspring dies25,41,51,57. Genetic overlap between depression and
anxiety and depressive symptoms seemed to be explained externalising phenotypes has been reported previously58,
by factors shared by siblings born of the same mother. and the generalist-gene hypothesis suggests that the same
Previous literature investigating the impact of drinking genes may pose genetic vulnerabilities toward multiple
during pregnancy on offspring internalising behaviours distinct psychiatric disorders.
shows mixed findings47, making it difficult to make firm After accounting for genetic relatedness, exposure to
conclusions on whether there is an environmental parental depression was associated with offspring exter-
association. nalising problems in several studies19–22,24,25,56, whereas
parental anxiety22 and overall internalising symptoms57
Offspring externalising behaviours were unrelated to offspring externalising behaviours.
Intergenerational transmission of externalising behaviours Combined with the findings described above, this indi-
Several adoption studies investigating the intergenera- cates that exposure to a depressed parent is a risk factor
tional transmission of externalising behaviours (Table 4) for both internalising and externalising behaviours. As
were based on the Early Growth and Development Study with childhood internalising problems, the association
(EGDS) sample. Detection of effects in these studies between maternal depression and childhood externalising
seemed to correlate with sample size, indicating that problems was often observed only in relation to con-
power considerations are important in interpreting these current depressive symptoms21,22,24, although one
results. In studies with fewer participants (up to 361 children-of-twins study reported an association between
families), birth parent externalising behaviour, antisocial prenatal maternal depression and ADHD in 5-year-olds56.
behaviour and self-regulation were uncorrelated with Current results mainly highlight that associations with
offspring externalising behaviours48–50, suggesting no prenatal depression in observational studies that do not
shared genetic effects. However, studies with more par- control for genetic effects are likely partly explained by
ticipants (561 families) showed correlations between birth unmeasured rGE. One adoption study investigating rGE
parent and offspring externalising behaviours51, and reported evocative effects; birth parent depression pre-
between birth parent antisocial behaviour and offspring dicted offspring externalising problems, which in turn
callous–unemotional behaviours52, although oppositional predicted adoptive parent depression19. As well as
and attentional-deficit behaviours were uncorrelated with demonstrating how genes and environment work in
birth parent antisociality52. Findings from previous lit- combination, the study highlights the bidirectional rela-
erature show substantial heritability of externalising tionship between parent and offspring mental health
behaviours3 and highlight the important role of genetic phenotypes.
transmission in explaining parent–offspring simarlity4. It
is likely that the detection of genetic transmission in Parenting behaviours
adoption studies requires more power, especially if the Genetic associations between parenting and offspring
specific parent and offspring phenotypes under investi- externalising behaviours were scarcely investigated (Table
gation are related, but not identical traits. 4). A children-of-twins study reported no genetic overlap
The role of environmental transmission in externalising between parental monitoring and offspring externalising
behaviours has also been previously implicated4. Here, we problems59, whereas an adoption study reported that birth
identified one adoption study which found no robust mother personality characteristics were partially asso-
evidence for an association between parent antisociality ciated with offspring callous–unemotional behaviours60.
and offspring disruptive behaviours53. In addition, three Previous children-of-twins studies show that it is plausible
large Swedish population-based studies of criminal that parents with a predisposition for negative parenting
behaviour found robust evidence of both genetic and behaviours have offspring predisposed to psychopathol-
environmental transmission of criminal behaviour8,54,55 ogy, and subsequently both phenotypes may share a
and showed that risk of criminal behaviour was strongest common aetiology4.
Table 4 Detailed characteristics of studies investigating offspring externalising behaviours (N = 36).
Offspring externalising behaviours
Study Design Sample Parental attribute Child attribute Control variables Genetic overlap Environmental transmission G–E interplay
(predictor) (outcome)
Bornovalova Adoption SIBS Antisociality: interview, SCI Maladaptive parenting: Mother and father age, Not studied Adoptive maladaptive Parental antisociality & child
et al.53 402 adoptive, 204 biological self-report, PEQ parental education, child parenting and marital discord disruptive behaviour disorders
families Marital discord: self-report ethnicity, child adoptive (but not antisociality) were were associated in biological
Age: 11–21 years or marital status, MRS status, family-based associated with offspring families, but not adoptive
Antisociality: clustering correction, disruptive behaviours families. The authors interpret
interview, SCI child sex, age this as passive rGE, but it may be
only indicative of genetic
overlap
Kendler et al.54 Adoption Snr Adoptive parental/sibling Criminal behaviour: Sex of the adoptee, birth The criminal behaviour of not- The criminal behaviour of No evidence of G × E
18,070 adoptees, and their criminal behaviour risk: register-based, any year, age at first lived-with biological parent and adoptive family and siblings was interaction found
biological (79,206) and composite score, criminal conviction cohabitation with siblings was associated with associated with offspring
adoptive (47,311) relatives behaviour, alcohol use adoptive parents offspring criminal behaviour criminal behaviour (OR range =
Age: adoption until 20 disorder (AUD), drug (OR = 1.5) 1.3–1.4)
years old abuse, psychiatric illness,
parental divorce
Biological parent/sibling
criminal behaviour risk:
composite score, criminal

behaviour, AUD, drug
abuse, psychiatric illness,
parental educational
attainment (EA), maternal
divorce, age at birth
Lipscomb et al.48 Adoption EGDS Adoptive parent over- Externalising behaviour: Prenatal and obstetric No, birth parent self-regulation Yes, over-reactive adoptive G×E: low birth parent self-
233 families reactive parenting: self- parent report, CBCL complications, birth did not predict offspring parenting was associated with regulation & exposure to early
Age: 9 months to 6 years report, PS mother IQ, adoptive externalising behaviours externalising behaviours care-centre × over-reactive
Birth parent self-regulation: family SES, adoption (β = 0.14) parenting: more externalising
self-report, ATQ openness, child age, sex, problems
age of entry & time
spent in early care
Kendler et al.55 Multiple parenting Snr Criminal behaviour: Criminal behaviour: Criminal behaviour Yes, criminal behaviour of not- Yes, criminal behaviour of
relationships design 2,111,074 intact, 155,121 not- Swedish Crime register Swedish Crime register status of all other lived-with biological parents adoptive or step-parent was
lived-with father, 10,194 not- relevant biological and was correlated with offspring correlated with offspring
lived-with mother, step-parents criminal behaviour (HR = 1.56) criminal behaviour (HR = 1.28)
107,163 stepfather,
17,637 stepmother, 10,038
adoptive families
Age: 15+
Kendler et al.8 Triparental family design Snr Criminal behaviour: Criminal behaviour: Yes, criminal behaviour of not- Yes, criminal behaviour of
41,360 triparental families Swedish Crime register Swedish Crime register lived-with biological parents adoptive or step-parent was
(mother, not-lived-with was correlated with offspring correlated with offspring
biological father, stepfather) criminal behaviour (HR = 1.46) criminal behaviour (HR = 1.30)
Age: 15+
Hyde et al.52 Adoption EGDS Adoptive mother positive Externalising behaviours: Child sex, openness/ Birth mother antisocial Adoptive mother positive G × E: high birth mother
561 families reinforcement: observation maternal report, CBCL contact in the adoption, behaviour predicted offspring reinforcement was protective antisociality × low adoptive
Age: 18–27 months Birth mother antisocial Callous - unemotional perinatal risk index callous–unemotional against callous–unemotional mother positive reinforcement:
behaviour: self-report, DIS behaviours behaviours (β = 0.16), but not (β = −0.19) and oppositional callous–unemotional
Oppositional behaviours oppositional or attention-deficit (β = −0.15), but not attention- behaviours
Attention-deficit behaviours deficit behaviours
behaviours
Stover et al.49 Adoption EGDS Marital hostility: self & Aggression: parent Adoption openness No, birth mother antisociality Adoptive parent hostile
361 families spouse-report, BARS report, CBCL was not associated with parenting and marital hostility
Age: 9 months to 6 years Hostile parenting: self- offspring aggression were associated with offspring
report, IFIRS aggression (β range = −0.5
Birth mother antisociality: to 0.09)
self-report, composite
score, delinquency (EYQ),
substance use (CIDI),
antisocial
behaviour (CDIS)
Page 19 of 38
Table 4 continued
Reuben et al.50 Adoption EGDS Warm parenting: self- Externalising behaviour: Prenatal risk and No, birth mother externalising Adoptive maternal warm
361 families report, IFIRS teacher-report, TRF obstetric complications, problems did not predict parenting (but not paternal, or
Age: 26 months to 7 years Over-reactive parenting: Effortful control: shape adoption openness, offspring externalising over-reactive parenting) was
self-report, PS Stroop task and gift delay birth mother behaviour or effortful control associated with offspring
Birth mother externalising task, the composite score externalising problems, externalising behaviours
problems: self-report, child sex (β = −0.18), and this association
composite score, was moderated by offspring
delinquency (ESBQ), effortful control
novelty seeking (TCI) and
drug dependence
Marceau et al.51 Adoption EGDS Adoptive parent warmth Conduct problems: Adoption openness, Birth mother externalising and Adoptive parent warmth and G × E: birth mother externalising
561 families and hostility: self- maternal report, child sex and earlier internalising problems were hostility were not associated problems × adoptive parent
Age: 4.5–8 years report, IWHS Preschool Age Psychiatric externalising problems associated with fewer conduct with offspring conduct warmth and hostility (boys only)
Birth mother substance use Assessment problems in boys (β range = problems after controlling for
during pregnancy: study −0.09 to −0.15) but not girls earlier externalising problems
design cannot distinguish
G and E effects
Birth mother internalising &
externalising problems:
composite score, number
of symptoms, diagnoses,
age of onset, first degree
relatives with
psychopathology
Marceau et al.41 Adoption EGDS Over-reactive parenting: Externalising behaviours: Adoption openness No, birth mother risk did not Yes, maternal (but not paternal)
361 families self-report, PS parent report, CBCL predict offspring externalising over-reactive parenting
Age: 9 months to 6 years Birth mother risk: self- behaviours (effect size not clear) predicted offspring internalising
report, composite score, behaviours (effect size not clear)
substance use, depression
(BDI) and anxiety (BAI)
McAdams et al.19 Adoption, children-of-twins Adoption: EGDS Adoptive & birth parent Externalising problems Adoption sample: Adoption sample: Birth mother Adoption sample: No, adoptive Evocative rGE: birth mother
361 families depression: self-report, BDI (adoption sample): parent Obstetric complications, depressive symptoms predicted parent depression did not depression predicted child
Age: 4.5–7 years Depressive symptoms (CoT report, CBCL adoption openness externalising problems at age predict subsequent offspring externalising problems, which
CoT: TOSS sample): self-report, CES-D Externalising problems CoT sample: twin 4.5 and 7 (β range = 0.13–0.16), externalising problems predicted adoptive parent
287 MZ and 489 DZ twin (CoT sample): mother, sex, age but not age 6 CoT sample: Yes, after depression
families father and self- CoT sample: No shared genetic accounting for genetic
Age: 11–22 years report, CBCL effects between parental relatedness, parental depression
depression and offspring was associated with offspring
externalising problems externalising problems (effect
size not clear)
Roos et al.57 Adoption EGDS Adoptive & birth mother Externalising-only Child sex, child age, Birth mother internalising Adoptive parent internalising G × E: adoptive mother high
293 families internalising symptoms: problems: parent adoption openness, symptoms and processing symptoms, uninvolved internalising symptoms x
Age: 6–7 years self-report, composite report, CBCL obstetric complications speed did not predict parenting, and processing inherited risk of slow processing
score, BAI and BDI Co-occurring internalising externalising-only symptoms, speed did not predict speed: co-occurring symptoms
Adoptive mother and externalising but maternal processing speed externalising-only problems, but
uninvolved parenting: self- problems: parent was associated with co- uninvolved parenting was
report, APQ report, CBCL occurring symptoms (OR = associated with co-occurring
Adoptive & birth mother 1.88) symptoms (OR = 7.91)
processing speed: Stroop
colour-word naming task
Grabow et al.20 Adoption EGDS, EPoCH Maternal trauma Externalising behaviours: EPoCH: timing of Yes, birth mother depression Adopted mother depression
541 adoptive mother–child frequency: repeated self- parent report, maternal trauma, SES, predicted adopted-away predicted offspring
pairs, 126 biological mother- report, mean score, NLES CBCL, age 7 child sex offspring externalising externalising behaviours (β =
biological child pairs Adoptive & birth mother EGDS: behaviours 0.40), and mediated the
Age: 7 years depressive symptoms: self- Perinatal risk, adoption (β = 0.22) relationship between maternal
report, BDI openness, SES, child sex trauma and offspring
externalising behaviours
Page 20 of 38
Table 4 continued
Gjerde et al.24 Sibling comparison MoBa Maternal depression: self- Externalising problems: Maternal parity, Not studied Children exposed to concurrent
11,599 families with 17,830 report, SCL maternal report, CBCL maternal EA, child age, maternal depression had more
full siblings child sex externalising symptoms than
Age: 6 months to 5 years their unexposed siblings, but
perinatal maternal symptoms
had no effect
Hannigan et al.21 Multiple children-of-twins MoBa Maternal depressive Externalising problems: Prenatal analyses: Yes, shared genetic effects No, after accounting for genetic
and siblings 22,195 mothers and 25,299 symptoms: self-report, SCL maternal report, CBCL adjusted for concurrent between maternal depression relatedness, maternal
children depression and offspring externalising depression was not associated
Age: 18–60 months problems explained 37% of the with offspring externalising
variance (R2) in offspring problems
externalising problems
Gjerde et al.22 Multiple children-of-twins MoBa Concurrent maternal Behavioural problems: Child sex, maternal age Yes, there were shared genetic Yes, after accounting for genetic
and siblings 22,316 mothers and 35,589 depression symptoms: self- maternal report, CBCL effects between maternal relatedness, maternal
offspring report, SCL depression and offspring depression was associated with
Age: 1.5 to 5 years behavioural problems offspring behavioural problems
(R2 = 14.2–29.3%) (R2 = 0.4–1.3%)

Hails et al.25 Adoption EGDS Adoptive parent depression: Externalising symptoms: Adoption openness, Yes, the birth mother’s Adoptive maternal (but not
561 families self-report, BDI-II parent and teacher prenatal risk and internalising symptoms paternal) depression predicted
Age: 9 months to 6 years Birth mother internalising report, CBCL and TRF obstetric complications, predicted parent (but not offspring externalising
symptoms: self-report, CIDI infant negative teacher) rated offspring symptoms
emotionality externalising symptoms (β = 0.11)
(β = 0.11)
Eilertsen et al.56 Children-of-twins and MoBa Parental prenatal ADHD symptoms: Yes, there were shared genetic After accounting for genetic
siblings 17,070 extended-family units depression symptoms: self- maternal report, CPRS effects between parental relatedness, maternal (but not
Age: 5 years reported at pregnancy depression and offspring ADHD paternal) prenatal depression
week 30 for mothers, symptoms (β = 0.42) was associated with offspring
week 17 for fathers, ADHD symptoms (β = 0.07)
Symptom Checklist
Gjerde et al.31 Sibling comparison MoBa Maternal anxiety Externalising problems: Child age, sex, maternal Not studied No difference in externalising
17,724 offspring and 11,553 symptoms: self-report, SCL maternal report, CBCL depressive symptoms, problems between exposed
mothers parity and education children and their unexposed
Age: 1.5–5 years siblings
Samek et al.64 Adoption SIBS Parent–child relationship Externalising behaviours: Child age, sex, Not studied Adoptive parent relationship The study states that it provides
525 adopted and 323 quality: offspring latent factor based on ethnicity, SES quality with child (but not evidence against passive rGE,
biological offspring report, PEQ antisocial behaviour (self- alcohol and tobacco use) was but in fact the adoption-at-birth
Age: 16.5 years and older Alcohol and tobacco use: report, SCI), risky sexual associated with offspring design excludes passive rGE
mother & father report, behaviour (self-report, externalising behaviours
composite score, SAM LEI) & alcohol and
and CSUA tobacco use (self-
report, SAM)
Elam et al.61 Adoption EGDS Adoptive parent hostility: Disruptive peer behaviour: Prenatal risk and Not studied Adoptive mother–child and Evocative rGE: birth mother low
316 families self-report, IFIRS parent report, PIPPS obstetric complications, father–child hostility predicted behavioural motivation
Age: 27 months to 4.5 years adoption openness offspring disruptive peer predicted toddler low social
behaviours motivation, which predicted
adoptive parent–child hostility
Marceau et al.59 Extended children-of-twins NEAD, TOSS Parental knowledge: Externalising problems: Age, sex, age difference No, there were no shared Yes, after accounting for genetic No passive or evocative
408 twin/sibling pairs, 854 mother, father and self- mother, father, and self- between non-twin genetic effects between relatedness, parental knowledge rGE found
twin families report, composite report, composite score, siblings and cousins parental knowledge and was associated with offspring
Age: 11–22 years score, CMS ZBPI (NEAD sample), offspring externalising problems externalising problems (effect
CBCL (TOSS sample) size not clear)
Guimond et al.65 Sibling comparison QNTS Perceived maternal support Delinquent behaviours: Genetically controlled Not studied No, perceived maternal support No evocative rGE, but child-to-
164 twin pairs and negativity: child self-report, S-RDQ analyses using MZ twin- and negativity were not parent effects found
Age: 13–14 years report, NRI difference score associated with offspring
delinquent behaviours
Plamondon Sibling comparison KFP Maternal negativity: self- Child disruptive behaviour: Maternal EA, child sex Not studied Exposed children showed more
et al.62 397 families, 920 children report, NLSCY mother and father report, and child age disruptive behaviours than their
Age: 1.5–4 years mean score, OCHS unexposed sibling
Page 21 of 38
Table 4 continued
Trentacosta Adoption EGDS Adoptive parent harsh Callous– unemotional Pregnancy and obstetric No difference in Adoptive parent harsh G × E: high inherited risk (high
et al.60 561 families parenting: self-report, PS behaviours: parent complications, adoption callous–unemotional parenting was associated with birth mother fearlessness and
Age: 18 months to 4.5 years Inherited risk: self-report, report, CBCL openness, child gender, behaviours in children with callous–unemotional low affiliation) × adoptive father
birth mother fearlessness oppositional behaviour high or low inherited risk behaviours at 54, but not at harsh parenting:
(BISS) and interpersonal 27 months (β range = callous–unemotional
affiliation (HAS-PP) 0.12–0.15) behaviours
Ellingson et al.71 Sibling comparison CNLSY Smoking during pregnancy: Disruptive behaviour: Maternal age at birth, Not studied No difference in disruptive
10,251 children of 4,827 self-report, mean number maternal report, BPI EA, intelligence, behaviours between exposed
mothers of packs smoked per day delinquency, offspring children and their unexposed
Age: 4–14 years sex, birth order, siblings
ethnicity, household
income, geographic
location
Kuja-Halkola Sibling comparison, Snr Maternal smoking during Criminality: national Maternal age at Yes, there were shared genetic No, exposed children did not
et al.67 children-of-twins 2,754,626 children pregnancy: self-report crime register, any childbirth, child sex, effects between maternal differ from their unexposed
Age: up to 20 years conviction birth year smoking during pregnancy and siblings, and after accounting
offspring criminality (effect size for genetic relatedness,

not clear) maternal smoking was not
associated with offspring
criminality
Kendler et al.66 Adoption Snr Drug abuse: Swedish ADHD: Hospital Yes, birth parent drug abuse No, adoptive or step-parent
1010 intact, 9944 triparental, medical registers, the Discharge Register, the was associated with offspring drug abuse was not associated
56,906 not-lived-with father, Suspicion Register, the Outpatient Care Register, ADHD (HR range = 2.06–2.48) with offspring ADHD
6141 not-lived-with mother, Crime Register, drug- and the Prescribed Drug
25,027 stepfather, related driving offenses, Register
5049 stepmother, 837 and the Prescribed Drug
adoptive families Register
Age: not reported
Obel et al.73 Sibling comparison DNR Maternal smoking during ADHD: diagnosis of Maternal age, parity, Not studied No difference in ADHD
Families of 17,381 children pregnancy: self-report hyperkinetic disorder, or child sex, year of birth diagnosis between exposed or
with ADHD prescription of ADHD unexposed siblings
Age: 3 years to diagnosis medication for at least
6 months
Knopik et al.72 Sibling comparison MO-MATCH study Smoking during pregnancy: ADHD symptoms: parent Maternal marital status Not studied Exposed children had more
173 mothers and their maternal report, MAGIC- and teacher-report, CRS at birth, food stamp parent-reported (but not
offspring PC usage at delivery, teacher-reported) ADHD
Age: 10–12 years exposure to paternal symptoms than their
smoking during unexposed siblings
pregnancy, childbirth
order, sex
Estabrook et al.70 Sibling comparison MIDS Maternal smoking during ADHD: SBSC Offspring age, sex, Not studied Exposed children were more
299 families pregnancy: self-report Oppositional Defiant parental history of likely to show oppositional
Age: 3–18 years Disorder (ODD): SBSC antisocial behaviour defiant disorder and conduct
Conduct Disorder (Antisocial Behaviour disorder (but not ADHD) than
(CD): SBSC Questionnaire) their unexposed siblings
Eilertsen et al.74 Sibling comparison MoBa Maternal alcohol use ADHD symptoms: Parental EA, parental Not studied Exposed children had more
16,407 mothers and 34,283 during pregnancy: AUDIT- maternal report, revised income, maternal ADHD symptoms (according to
children C CRS and CBCL smoking during CPGS-R, but not CBCL) than
Age: 5 years ADHD diagnosis: pregnancy, children’s their unexposed siblings, but
diagnosis birth order, gender did not differ in ADHD
diagnosis
Lund et al.47 Sibling comparison MoBa Maternal alcohol Behavioural problems: Parity, unplanned Not studied Exposed children were more
14,639 mothers, 25,744 consumption during maternal report, CBCL pregnancy, daily aggressive, but did not have
children pregnancy: self-report, Attention problems smoking, pre-pregnancy more attentional problems,
Age: 1.5–5 years AUDIT-C Aggressive behaviours abstinence from alcohol than their unexposed sibling
Page 22 of 38
Table 4 continued
Pingault et al.13 Within-family PGS: genetic TEDS Maternal EA: self-report, ADHD: maternal, report, Sex, age and ten Yes, the association between Under a twin-heritability
sensitivity analysis 3663 to 4693 individuals eight levels mean score, CRS-Revised principal components of maternal EA and offspring scenario, the association
Age: 8–16 years ancestry, PGS for EA ADHD decreased after adjusting between maternal EA and
and ADHD for EA and ADHD PGS (from offspring ADHD was expected
β = −0.13 to β = −0.11) to be null if EA and ADHD PGS
captured all heritability
Torvik et al.45 Children-of-twins and MoBa Educational attainment: ADHD symptoms: Yes, there were shared genetic Yes, after accounting for genetic
siblings 34,958 children self-report, highest level maternal report, RSDBDs effects between parental EA relatedness, parental EA was
Age: 8 years completed and offspring ADHD symptoms associated with offspring ADHD
(effect size not clear) (effect size not clear)
de Zeeuw et al.75 Within-family PGS: genetic NTR Genetic transmission: effect ADHD symptoms: parent Sex, year of birth (for EA), EA and ADHD PGS based on EA and ADHD PGS based on
nurture (transmitted/non- 5900 offspring, of transmitted alleles PGS and teacher report, at- the interaction between transmitted parental alleles non-transmitted parental alleles
transmitted method) 2649 families for EA and ADHD home and at-school sex and year of birth (for were associated with offspring were not associated with
Age: 10–12, 25–64 years Genetic nurture: effect of symptoms, CBCL and TRF EA), ten principal ADHD symptoms at home and offspring ADHD symptoms at
non-transmitted alleles components, at school (R2 = 0.8–2%) home and at school
PGS for EA and ADHD genotyping platform
G–E gene–environment, G×E gene–environment interaction, rGE gene–environment correlation.

Design = CoT children-of-twins, PGS polygenic scores.
Samples = CNLSY Children of the National Longitudinal Survey of Youth, EGDS Early Growth and Development Study, Dnr Danish national registers, EPoCH Early Parenting of Children study, MIDS Midwest Infant
Development Study, KFP Kids, Families, and Places Study, MoBa Norwegian Mother Father and Child Study, MO-MATCH Missouri Mothers and Their Children Study, NEAD Nonshared Environment in Adolescent Development
Study, NTR Netherlands Twin Register, QNTC Quebec Newborn Twin Study, SIBS Sibling Interaction and Behaviour Study, Snr Swedish national registers, TEDS Twins Early Development Study, TOSS Twin Offspring Study of
Sweden.
Measures = APQ Alabama Parenting Questionnaire, ATQ Adult Temperament Questionnaire, AUDIT-C Alcohol Use Disorder Identification Test-Consumption, BAI Beck Anxiety Inventory, BARS Behaviour Rating Scale, BDI Beck
Depression Inventory, BISS Behavioural Inhibition System scale, BPI Behaviour Problem Index, CBCL Child Behaviour Checklist, CDIS Computerised Diagnostic Interview Schedule, CES-D Centre for Epidemiological Studies
Depression Scale, CIDI Composite International Diagnostic Instrument, CMS Child Monitoring Scale, CRS Conner’s Rating Scale, CSUA Computerised Substance Use Assessment, DIS Diagnostic Interview Schedule, ESBQ Elliott
Social Behaviour Questionnaire, EYQ Elliott Youth Questionnaire, HAS-PP Harter Adult Self-Perception Profile scale, IFIRS Iowa Family Interaction Rating Scales, IWHS Iowa Warmth and Hostility Scales, LEI Life Events Interview,
MAGIC-PC Missouri Assessment of Genetics Interview for Children–Parent on Child, MRS Marital Relationship Questionnaire, NLES Negative Life Events Scale, NRI Network of Relationships Inventory, NLSCY negativity scale
from the National Longitudinal Survey of Children and Youth, OCHS conduct disorder-aggression scale from the Ontario Child Health Study, PEQ Parental Environment Questionnaire, PIPPS Penn Interactive Peer Play Scale, PS
the Parenting Scale, RSDBD Rating Scale for Disruptive Behaviour Disorders, SAM Substance Abuse Module, SBSC Stony Brook Symptom Checklist, SCI Structured Clinical Interview for DSM-III-R, SCL Symptoms Checklist, S-RDQ
Self-Report Delinquency Questionnaire, TCI Temperament Characteristic Inventory, TRF Teacher Report Form, ZBPI Zill Behaviour Problems Inventory.
Statistics = β standardised parameter estimate, OR odds ratio, HR hazard ratio, R2 percentage of variance explained. Effect sizes are not reported for studies that did not investigate both genetic and environmental
transmission.
Page 23 of 38
Studies of environmental transmission found associa- not associated with ADHD diagnosis in a large
tions between both positive and negative parenting and population-based sample73. Exposure to maternal alcohol
offspring externalising behaviours. Negative parenting use during pregnancy was linked to offspring aggression
behaviours were associated with increased offspring in one study47, and to offspring ADHD symptoms in
externalising behaviours49,53,60–62, but these effects were another74, but the latter association was not reliably
sometimes inconsistent across raters. For instance, over- observed across measurement instruments, and more-
reactive parenting was associated with parent-rated41,48, over, maternal drinking was not associated with ADHD
but not teacher-rated50 externalising problems. This diagnosis74 or attentional problems47. Studies of parental
could reflect differences in the child’s behaviour observed substance use during childhood found no environmental
at home by the parent, or at school by the teacher. effect of parent alcohol and tobacco use64 or drug abuse66
Alternatively, these differences could be indicative of rater on offspring externalising behaviours. The overall pattern
biases resulting from differences in the interpretation of of results indicates that prenatal exposure to substance
scale items, a unique perception of the children’s beha- use may be associated with some offspring externalising
viour, or the rater’s own mental health63. More research is behaviours, but no firm conclusions can be drawn from
required to clarify rater-specific findings. Focusing on current or previous work.
positive parenting, factors such as parental knowledge of
offspring whereabouts, good parent–child relationship
quality, positive reinforcement, and warm parenting were Parental education attainment
associated with fewer externalising problems50–52,59,64, Three studies found evidence of genetic overlap
whereas there were no associations between parental between parental education attainment and offspring
positive reinforcement and ADHD symptoms52, or ADHD symptoms13,45,75 (Table 4). Genetic overlap
maternal support and offspring delinquent behaviour65. between educational attainment and ADHD is previously
Investigation of possible gene-environmental correlation known76, and is hypothesised to either suggests a com-
between parenting and offspring externalising behaviours mon neurobiological process underlying both inattention
in adoption samples found no passive or evocative rGE symptoms and academic achievement, or an indirect
effects in the associations between parental knowledge mechanism through which genetically influenced inat-
and offspring externalising behaviours59, whereas one tention impacts academic achievement77. Both of these
study reported an evocative rGE showing that parental scenarios are feasible in the context of the observed
hostility was evoked by genetically influenced offspring parent–offspring associations.
behaviour61, and another reported child-to-parent effects Findings for an environmental pathway were mixed.
on maternal support and negativity65. As well as high- Although a within-family PGS study estimated that the
lighting the bidirectionality of parent–offspring associa- association between maternal education and offspring
tions, these studies show that associations between ADHD would be null after adjusting for PGS that cap-
parenting and offspring outcomes vary by phenotype and tured all heritability based on twin-based estimates13, a
no single explanation fits all parenting–offspring large children-of-twins study found that maternal edu-
associations. cation was associated with offspring ADHD symptoms
even after accounting for genetic relatedness45. Parental
Parental substance use educational attainment has been associated with specific
Two studies reported that parental drug abuse66 and parenting styles78, and it seems plausible that these par-
smoking67 shared genetic overlap with offspring exter- enting behaviours subsequently influence offspring
nalising behaviours (Table 4). These reports of genetic ADHD. However, based on what we know from twin
overlap are in line with classical twin studies which sug- literature, where ADHD shows very high heritability, and
gest that comorbidity between substance use and exter- little effects of the shared or unique environments3, the
nalising behaviours is partly due to overlapping genetic overall impact of parenting behaviours on ADHD is likely
factors68,69. After accounting for genetic relatedness, to be small.
mixed evidence for environmental associations between
parental substance use and some offspring externalising
behaviours was found. Maternal smoking during preg- Genetic nurture
nancy was linked to offspring oppositional defiant dis- One within-family PGS study of ADHD found no
order70 and conduct problems70, whereas a larger study genetic nurturing effect on offspring ADHD due to
showed no association with offspring disruptive beha- ADHD or educational attainment related to parental
viours71. Similarly, smoking during pregnancy was asso- genes75. Although this finding requires replication, it is
ciated with parent-reported ADHD symptoms in one compatible with what we know from twin-based litera-
sibling comparison study72, but not another70, and was ture, discussed above.
Offspring educational attainment where parental PGS of educational attainment was more
Intergenerational transmission of educational attainment strongly associated with offspring educational attain-
Studies investigating intergenerational educational ment in biological families than adoptive families85. This
attainment showed consistent evidence of genetic overlap particular passive rGE has also been reported outside of
between parent and offspring educational attain- the reviewed work91.
ment13,45,79–81 (Table 5). Additional evidence of genetic
transmission was provided by several within-family PGS
studies showing that parental genetic liability for educa- Maternal smoking during pregnancy
tional attainment predicted offspring educational attain- A large children-of-twins study reported genetic
ment13,75,82–85. After accounting for genetic relatedness, overlap between maternal smoking during pregnancy
evidence of environmental transmission of intergenera- and offspring general cognitive ability67 (Table 5). This
tional educational attainment was observed in several finding is in line with the known negative genetic cor-
studies45,79–82. Taken together, current literature indicates relation between smoking and educational attainment92
that as well as passing on education-associated genes, and highlights that in observational studies without
parents may shape the rearing environment in a way that genetically informative designs, this parent–offspring
influences the offspring’s subsequent educational attain- association explained by unmeasured genetic effects
ment. However, these environment influences may could lead to spurious conclusions. Investigations of
nonetheless be partly influenced by parental genes. In line environmental transmission did not reveal robust asso-
with this, a within-family PGS study provided evidence of ciations; maternal smoking during pregnancy was nega-
passive rGE, showing that individuals with higher PGS for tively associated with reading cognition71, but
educational attainment tended to grow up in better- associations with other measures of cognitive function-
educated households than those with lower PGS86. ing71, general cognitive ability67, and academic achieve-
ment67 did not remain after accounting for genetic
Genetic nurture relatedness. Previous literature on genetically informa-
Research into genetic nurture has gained traction in the tive designs suggests that familial factors, including
last two years, starting with the publication of three land- genetic effects, account for the relationship between
mark studies with novel designs to identify genetic nur- smoking during pregnancy and offspring cognition93.
turing effects on offspring educational attainment14,83,87
(Table 5). These studies have highlighted that parental Offspring substance use
genes can have an indirect (environmentally mediated) Intergenerational transmission of substance use behaviours
effect on offspring educational attainment through parental Studies investigating intergenerational transmission of
traits that are genetically influenced. The genetic nurturing substance use behaviours (Table 6) showed consistent
effect on offspring educational attainment has been repli- evidence of genetic transmission of substance involve-
cated in several samples15,75,78,84–86,88,89, and a few studies ment94, alcohol use9,95–97, drug abuse8,9,98,99 and smoking
reported that the observed effect was partly explained by initiation100. There was also evidence of environmental
family socioeconomic status14,15,89. This finding is com- transmission of many substance use behaviours, including
patible with an adoption study which found that adoptive drinking behaviour101, alcohol use disorder8,9,95,97, drug
parents with higher income had offspring with increased abuse8,9,11,98,99,102, smoking behaviour100,103 and
educational attainment90. Other studies reported addi- 104
addiction-prone personalities , whereas parental
tional mediating effects of parental IQ88, maternal dependency on alcohol was not consistently associated
health during pregnancy89 and parenting behaviours78. with offspring alcohol involvement94,96. Two studies
The last study was the first to show that specific par- showed no long-term effects of maternal smoking during
enting behaviours are under the genetic influence of pregnancy on offspring substance use behaviours67,105.
education-associated genes, and that these genetically Although parental substance use behaviours were gen-
influenced parenting behaviours are subsequently asso- erally associated with an increased likelihood of substance
ciated with offspring educational attainment. In addi- use in offspring, an extended twin study observed negative
tion, the study reported evidence of passive rGE, as environmental transmission of smoking behaviours,
mothers with higher PGS for education attainment whereby parental smoking had an inhibiting effect on
provided home environments that were more conducive offspring smoking initiation103. The finding was margin-
to higher educational attainment (greater cognitive sti- ally significant and requires replication. One study found
mulation, more warm and sensitive parenting, and less evidence of passive rGE underlying parent–offspring
chaotic and safer, tidier homes)78. Evidence of passive similarity in drinking behaviours, with more similarities in
rGE was also found for the overall genetic nurturing biological parent–child relationships than in adoptive
effect in a within-family PGS study of adoption samples, families106.
Table 5 Detailed characteristics of studies investigating offspring educational attainment and cognition (N = 21).
Offspring educational attainment and cognition
Kendler et al. Adoption Snr EA: highest education IQ: Military Conscription Clustering of siblings Not studied Yes, adoptive parent EA
124
(siblings-reared- 436 sibships, one achieved by both parents, Register, within biological families predicted offspring IQ
apart) member reared by five-point-scale standardised test
biological, other by
adoptive parents
Age: 18–20 years
Conley et al.82 Within-family PGS: FHS, HRS Parental education EA: self-report, highest Child sex, age Yes, parental EA PGS Genetic sensitivity No G × E interaction
genetic sensitivity 6186 individuals from Genetic transmission: effect grade completed predicted offspring EA analysis: After controlling found between
analysis, and 4867 households of parental EA PGS (effect size not clear) for offspring EA PGS, maternal EA and
genetic nurture Mean age: 39.49 years Genetic nurture: effect of parental EA was still offspring PGS
(statistical control (FHS), 68.17 years (HRS) parental EA PGS, after associated with offspring
method) adjusting for child EA PGS EA. Genetic nurture: no
evidence of genetic
nurture as parental EA
PGS was not associated

with offspring EA after
controlling for offspring
EA PGS (effect size
not clear)
Ayorech Extended twin, TEDS EA (extended twin): self- EA: self or parent report, PGS analyses: previous Twin analyses: yes, additive Twin analyses: yes, shared
et al.79 within-family PGS Twin analyses: 6105 reported highest A levels qualification school performance genetic effects underlying environmental effects
twin pairs qualification Intergenerational EA (GCSE grades) intergenerational EA were underlying
PGS analyses: 5825 Genetic transmission (extended twin): found (R2 = ~50%) intergenerational EA
individuals (within-family PGS): effect similarity between PGS analyses: yes, parental were found (R2 = ~40%)
Age: 18 years of parental EA PGS parental and offspring EA PGS was associated with PGS analyses: Not studied
EA, two levels intergenerational EA
Intergenerational EA
(within-family PGS):
similarity between
parental and offspring
EA, four levels
Scheeren Adoption NLnr EA: register-based, highest EA: level of enrolment Father and mother year Not studied Adoptive parents’ Passive rGE: family
et al.90 1792 adopted children, education level in secondary school, of birth, family structure, income (but not EA) income was more
424,928 biological Parental income: yearly four levels number of children in predicted offspring EA strongly associated with
children household income the household, offspring EA in
Age: 15 years observation year, biological families than
adoption age, country of adoptive families
adoption, gender
Bates et al.14 Within-family PGS: BATS Genetic nurture: effect of EA: Queensland Core Sex, age at test, Not studied PGS for EA based on No G × E interaction
genetic nurture 2,335 children and their EA PGS based on non- Skills Test offspring EA PGS non-transmitted alleles found between PGS
(transmitted/non- genotyped parents transmitted alleles were associated with and SES
transmitted Age: 17 years SES: ASI-2006 offspring EA, but this
method) relationship disappeared
after adjusting for
parental SES
Belsky et al.86 Within-family PGS: E-RISK, NLAAH Genetic nurture: effect of EA: GCSE attainment; Genetic principal Not studied Yes, parental EA PGS was Passive rGE: individuals
genetic nurture 1574 & 5526 individuals parental EA PGS, after four levels components associated with offspring with higher PGS grew
(statistical control Age: 18 years, late 20 s to adjusting for child EA PGS EA after adjusting for up in better-educated
method) early 30 s offspring EA PGS households
Page 26 of 38
Table 5 continued
Kong et al.83 Within-family PGS: deCODE Genetic transmission: effect EA Sex, year of birth, the Yes, EA PGS based on Yes, EA PGS based on
genetic nurture 21,637 probands with at of EA alleles PGS based on interaction between sex transmitted parental alleles non-transmitted parental
(transmitted/non- least one transmitted alleles and year of birth, 100 was associated with alleles was associated
transmitted genotyped parent Genetic nurture: effect of principal components offspring EA (direct effect with offspring PGS
method) Age: not reported EA PGS based on non- explained 70% of the overall (genetic nurture
transmitted alleles observed effect of EA PGS) explained explaining
22.4% of the overall
effect of EA PGS)
Liu et al.84 Within-family PGS: FHS, HRS Genetic transmission (FHS EA 7 principal components Yes, parental EA PGS was Yes, parental EA PGS was
genetic nurture 8639 individuals from sample): effect of FHS: self-report, years of HRS sample: associated with offspring EA associated with offspring
(statistical control three generations and parental EA PGS education completed child’s EA PGS (FHS sample; β = 0.345), and EA, after adjusting for
method) 9342 individuals Genetic nurture (FHS HRS: parent report offspring EA PGS attenuated offspring EA PGS (β =
over age 50 sample): effect of parental the association between 0.076)
Age: not reported EA PGS, after adjusting for parental and offspring EA
child PGS (HRS sample; from β = 0.314

EA (HRS sample): self- to β = 0.292)
report, years of education
Young et al.17 Relatedness deCODE Genetic nurture: estimated Educational attainment: Sex, year of birth Not studied Yes, after accounting for
disequilibrium 12,035 individuals who variance in offspring trait self-report, number of shared genetic effects,
regression had parents and explained by parental years of schooling parental genes explained
grandparents genotyped genes acting indirectly via variance in offspring EA
Age: not reported the environment
Pingault Within-family PGS: TEDS Maternal EA: self-report, EA: mean of three Sex, age and ten Yes, association between Under a twin-heritability
et al.13 genetic sensitivity 3663–4693 individuals eight levels standardised tests principal components of maternal EA and offspring scenario, the association
analysis Age: 8–16 years ancestry, PGS for EA EA decreased after adjusting between maternal and
for EA PGS (from β = 0.40 offspring EA was
to 0.33) expected to be null if EA
PGS captured all
heritability
Bates et al.15 Within-family PGS: BATS Genetic nurture: effect of EA: Queensland Core Sex, age at test, Not studied PGS for EA based on No G × E interaction
genetic nurture 2335 children and their parental EA PGS based on Skills Test offspring EA PGS non-transmitted alleles found between PGS
(transmitted/non- genotyped parents non-transmitted alleles were associated with and SES
transmitted Age: 17 years SES: ASI-2006 offspring EA, but this
method) relationship disappeared
after adjusting for
parental SES
Willoughby Within-family PGS: MCTFR Genetic nurture: effect of Years of education: self- Height and BMI used as Not studied Yes, parental EA PGS was
et al.88 genetic nurture 1223 families, 2446 parental EA PGS, on top of report, mean age 29 negative controls associated with offspring
(statistical control offspring child EA PGS High-school grade- EA traits after adjusting
method) Age: varied SES: composite score, point-average: self- for offspring EA PGS, and
family income, parent report, age 17 this association was
education level, parent IQ: WIS, mean age 14.4 mediated by parental
occupation level SES and IQ
Parental IQ: WIS
Page 27 of 38
Table 5 continued
Armstrong- Within-family PGS: BiBs Genetic nurture: effect of Academic performance: Child EA PGS, maternal Not studied Yes, maternal EA PGS was
Carter et al.89 genetic nurture 2077 mother–child dyads maternal EA PGS, after standardised age, first ten principal associated with offspring
(statistical control Age: 7 years adjusting for child EA PGS national exam components academic performance,
method) Maternal health: after adjusting for
composite score, self- offspring EA PGS, and this
reported mental health, association was
smoking, indirect smoke mediated by maternal
exposure, alcohol and health and SES during
drug use, vitamin use, pregnancy
sleep problems, and BMI
SES: composite score, self-
reported education,
cohabitation status,
employment, maternity
leave, governmental
benefits, perceived
financial difficulty, and
governmental index of
neighbourhood-level
deprivation
Borriello Adoption EGDS Mathematical achievement: Mathematical Obstetric complications, Yes, birth parent and Yes, paternal (but not No G × E
et al.80 195 families standardised scores on the achievement: adoption opennness, offspring mathematic maternal) mathematic interaction found
Age: 7 years mathematics fluency standardised scores on parent education level, achievement were achievement was
subtest of WJ-III the mathematics non-mathematical correlated (β = 0.17) correlated with adopted-
fluency subtest of the cognitive skills offspring mathematical
WJ-III achievement (β = 0.15)
Domingue Adoption WLS Genetic transmission: Educational attainment: Child sex, age, ten Yes, parental EA PGS was Yes, parental EA PGS was Passive rGE implied:
et al.85 (PGS study) 855 adopted and 20,939 association between parent-reported, principal components associated with EA of associated with EA of higher association in
biological offspring parental EA PGS and EA of highest grade of school biological offspring (effect adoptive offspring (effect biological families than
Age: not reported biological offspring attended size not clear) size not clear) adoptive families
Genetic nurture: association
between parental EA PGS
and EA of adoptive
offspring
de Zeeuw Within-family PGS: NTR Genetic transmission: effect Childhood academic Sex, birth year (EA), EA PGS based on EA PGS based on non-
et al.75 genetic nurture 5900 offspring from 2649 of EA and ADHD ADHD achievement: interaction between sex transmitted parental alleles transmitted parental
(transmitted/non- families PGS based on transmitted nationwide and birth year (EA), ten were associated with alleles were associated
transmitted Age: 10–12, 25–64 years alleles standardised test principal components, offspring academic with offspring EA in
method) Genetic nurture: effect of at age 12 genotyping platform achievement in childhood adulthood (R2 = 1.7%),
EA and ADHD PGS based Adult EA: self-report, and EA in adulthood (R2 = but not academic
on non-transmitted alleles highest degree; 5.7–7.6%) but there was no achievement in
four levels association with ADHD PGS childhood (which was
also not associated with
non-transmitted PGS
for ADHD)
Halpern- Adoption EGDS Adoptive and birth parent Early educational Obstetric complications, Yes, birth parent EA was Yes, adoptive parent EA No G × E interaction
Manners 340 families education attainment: self- achievement: WJ-III adoption opennness, associated with offspring EA was associated with
et al.81 Age: first-graders report, highest level of child sex, child and (effect size not clear) offspring EA (effect size
(6–7 years) education completed by adoptive parents’ not clear)
adoptive or birth parents ethnicity, adoptive
Page 28 of 38
Table 5 continued
parents’ age, type of

adoption agency
45
Torvik et al. Children-of-twins MoBa Educational attainment: Academic problems: Yes, there were shared Yes, after accounting for
and siblings 34,958 children self-report, highest level maternal report, three- genetic effects between genetic relatedness,
Age: 8 years completed point scale parental EA and offspring parental EA was
academic problems (effect associated with offspring
size not clear) academic problems
Ellingson Sibling CNLSY Smoking during pregnancy: Cognitive functioning: Maternal age at birth, EA, Not studied Exposed children had
et al.71 comparison 10,251 children of 4827 self-report, mean number PPVT-R (math, reading intelligence, poorer reading
mothers of packs smoked per day and reading delinquency, offspring recognition than their
Age: 4–14 years Recognition subtests) sex, birth order, ethnicity, unexposed siblings, but
and digit span test household income, there were no other
geographic location group differences
Kuja-Halkola Sibling Snr Maternal smoking during Academic achievement: Maternal age at Yes, there were shared No, exposed children did
et al.67 comparison, 2,754,626 children pregnancy: self-report class 9 records childbirth, child sex, genetic effects between not differ from their
children-of-twins Age: up to 20 years General cognitive ability: birth year maternal smoking during unexposed siblings, and
Military Conscription pregnancy and offspring EA after accounting for
Register, nine levels traits (effect size not clear) genetic relatedness,
maternal smoking was
not associated with
offspring EA traits
Wertz et al.78 Within-family PGS: E-RISK Genetic nurture: effect of EA: self-report, highest Sex, first ten principal Yes, controlling for offspring Genetic nurture: yes, Evocative rGE: mother
genetic nurture 860 mothers and their maternal EA PGS, after educational attainment, components, EA PGS attenuated the maternal EA PGS was and offspring PGS for
(statistical control children adjusting for child PGS 18 years offspring EA PGS association between associated with offspring EA predicted cognitive
method) Age: 18 years Parenting behaviour: parenting behaviours and EA after adjusting for stimulation and warm,
mother, child and offspring EA (from β offspring EA PGS (β = sensitive parenting
interviewer report, range = 0.33–0.52 to β 0.11), and this effect was
cognitive stimulation, range = 0.30–0.48) mediated by parenting
warmth and sensitivity, behaviours including
household chaos, and cognitive stimulation,
safety and tidiness of the household chaos and a
family home safe, tidy home (but not
parental warmth)

Design = PGS Polygenic scores.
Samples = BATS Brisbane Adolescent Twin Study, BiBs Born in Bradford study, CNLSY Children of the National Longitudinal Survey of Youth, EGDS Early Growth and Development Study, deCODE Icelandic Genealogy
Database, FHS Framingham Heart Study, HRS Health Retirement Study, MoBa Norwegian Mother Father and Child Study, MCTFR Minnesota Centre for Twin and Family Research, NLNR Dutch national registers, NLAAH
National Longitudinal study of Adolescent to Adult Health, NTR Netherlands Twin Register, SNR Swedish national registers, TEDS Twins Early Development Study, WLS Wisconsin Longitudinal Study.
Measures = ASI Australian Socioeconomic Index occupational status scale, PPVT-R Peabody Picture Vocabulary Test-Revised, QCST Queensland Core Skills Test, WIS Weschler Intelligence Scale, WJ-III Woodcock–Johnson Test
of Achievement III.
Statistics = β standardised parameter estimate, R2 percentage of variance explained. Effect sizes are not reported for studies that did not investigate both genetic and environmental transmission.
Page 29 of 38
Table 6 Detailed characteristics of studies investigating offspring substance use behaviours (N = 19).
Offspring substance use behaviours
McGue Adoption SIBS Drinking behaviour: self-report, Drinking behaviour: self- Parent gender, and Not studied Yes, adoptive parent drinking Passive rGE implied:
et al.106 409 adoption and 208 biological composite score, CSUA report, composite score, child gender behaviour was associated with parent–offspring association
families and SAM CSUA and SAM offspring drinking behaviour was greater in biological
Age: 10–28 years pairs than adoptive pairs
Waldron Children-of-twins MATCH, PACER Substance dependence: self- Offspring substance Parent or offspring comorbid Substance dependence: Substance dependence: after
et al.94 1318 offspring of twin parents report, SAGA involvement: self- psychopathology, twin sex, yes, there were shared accounting for genetic
Age: 11–24 years Parental separation: study report, SAFA twin age, twin EA, child genetic effects between relatedness, parental substance
design cannot distinguish G sex, age parental substance dependence was not associated
and E effects dependence and with offspring substance
offspring substance involvement with the exception
involvement (effect size of cannabis use which was
not clear) associated with offspring
smoking behaviour (effect size
not clear)
Kuja-Halkola Sibling comparison, Snr Maternal smoking during Drug/alcohol misuse: Maternal age at childbirth, Yes, there were shared No, exposed children did not
et al.67 children-of-twins 2,754,626 children pregnancy: self-report register-based, diagnosis, child sex, birth year genetic effects between differ from their unexposed
Age: up to 20 years or drug-related maternal smoking siblings, and after accounting

conviction during pregnancy and for genetic relatedness,
offspring drug/alcohol maternal smoking was not
misuse (effect size associated with offspring drug/
not clear) alcohol misuse
Kendler Adoption Snr AUD: Swedish Hospital AUD: Swedish Hospital Yes, birth parent AUD Yes, adoptive parent AUD No G × E interaction
et al.95 18,115 adoptees, 171,989 not-lived- Discharge Register, the Discharge Register, the predicted offspring AUD predicted offspring AUD (OR = observed
with parent, and 107,699 step- Swedish Prescribed Drug Swedish Prescribed Drug (OR = 1.46) 1.40)
parent families Register, the Outpatient Care Register, the Outpatient
Mean age: 33.9 years Register, the Primary Health Care Register, the
Care Register, and the Primary Health Care
Swedish Crime and Suspicion Register, and the
Register Swedish Crime and
Suspicion Register
Grant et al.96 Children-of-twins VET Parental alcohol or drug Alcohol involvement: self- Maternal alcohol dependency, Substance dependency: Substance dependency: yes,
1828 offspring of male twin parents dependency: diagnosis, DIS report, SAGA heavy cannabis use, family yes, there were shared after accounting for genetic
Age: not reported Parental separation: study income, child sex, age, history genetic effects between relatedness, parental substance
design cannot distinguish G of psychiatric problems and parental substance dependency was associated
and E effects traumatic life events, dependence and with offspring alcohol
inattention, hyperactivity and offspring alcohol involvement (effect size
oppositional defiant disorder involvement (effect size not clear)
not clear)
Kendler Triparental family design Snr Drug abuse: medical registries, Drug abuse: medical Yes, drug abuse and Yes, drug abuse or AUD
et al.8 41,360 triparental families (mother, the Crime Register, the registries, the Crime AUD registration of not- registration of adoptive or step-
not-lived-with biological father, Suspicion Register, drug- Register, the Suspicion lived-with biological parent correlated with offspring
and stepfather) related driving offences, and Register, drug-related parents were correlated drug abuse or AUD (HR range
Age: 15+ the Prescribed Drug Register driving offences, and the with offspring drug = 1.27–1.99)
AUD: medical and mortality Prescribed Drug Register abuse and AUD (HR
registries, the Suspicion AUD: medical and range = 1.84–2.45)
Register, the Crime Register, mortality registries, the
and the Prescribed Drug Suspicion Register, the
Register Crime Register, and the
Prescribed Drug Register
Kendler Triparental family design Snr Drug abuse: medical registers, Drug abuse: medical Drug abuse status of all other Yes, drug abuse Yes, drug abuse behaviour of
et al.98 2,111,074 offspring in intact families the Crime Register, the registers, the Crime relevant biological and step- behaviour of not-lived- adoptive or step-parent
155,121 not-lived-with father, Suspicion Register, and drug- Register, the Suspicion parents with biological parents correlated with offspring drug
10,194 not-lived-with mother, related driving offences Register, and drug- were correlated with abuse (HR = 1.79)
107,163 stepfather, related driving offences offspring drug abuse
17,637 stepmother 10,038 adoptive (HR = 2.73)
families
Age: 15+
Page 30 of 38
Table 6 continued
Bidwell Sibling comparison MO-MATCH Smoking during pregnancy: Substance use: self- Maternal age, marital status, Not studied No difference in substance use
et al.105 173 mothers and their offspring self-report, MAGIC-PC report, DUSI EA, qualification for food behaviours between exposed
Age: 7–15 years stamps at the time of delivery, children and their unexposed
parental substance use outside siblings
of pregnancy, childbirth order,
sex, exposure to paternal
smoke during pregnancy
Kendler Extended family design Snr AUD: medical registries, the AUD: medical registries, AUD in the biological mother, Yes, not-lived with Yes, stepfather AUD (including
et al.97 38,373 offspring of not-lived-with Prescribed Drug Register, two the Prescribed Drug and offspring sex father AUD (including the number of registrations that
fathers and 9711 offspring of step- or more convictions of drunk Register, two or more age of registration, occurred while co-offspring
fathers driving in the Crime register convictions of drunk recurrence and number with offspring) predicted
Age: 15+ driving in the Crime of AUD registrations) offspring AUD (HR = 1.03)
register predicted offspring AUD
(HR not reported)
Treur et al.100 Children-of-twins, within- NTR Smoking initiation (CoT CoT sample smoking CoT: twin sex, twin age, child CoT sample: yes, there CoT sample: yes, after G×E: high PGS for smoking
family PGS: genetic CoT sample: 712 twins, 723 sample): self-report initiation: self-report sex, age, family-based were shared genetic accounting for genetic initiation & heaviness ×
sensitivity analysis children Exposure to smoking (PGS PGS sample smoking clustering correction effects between parent relatedness, parent smoking childhood exposure to
PGS sample: 4072 individuals sample): offspring-reported behaviour: self-report, PGS: sex, year of birth, ten and offspring smoking initiation was associated with smoking: smoking heaviness
Age: not reported exposure as a child (up to smoking initiation and principal components, family initiation (effect size offspring smoking initiation (no interaction for smoking
age 18) smoking heaviness clustering correction not clear) (effect size not clear) initiation)
PGS sample: not studied PGS sample: yes, after adjusting
for smoking PGS, exposure to
smoking during childhood was
associated with smoking
initiation (OR = 1.68)
Maes et al.103 Extended twin V-30, A-25 22,393 twins and their Smoking initiation: self-report Smoking initiation: self- Age Not studied There were shared Passive rGE: negative
families report environmental effects covariance between additive
Age: 18+ underlying parent–offspring genetic effects and parental
similarity in smoking initiation smoking
(negative cultural transmission)
Kendler Multiple parenting Snr Drug abuse: medical and Drug abuse: medical and Yes, drug abuse Yes, drug abuse behaviour of
et al.99 relationships design 2,111,074 intact, 41,360 triparental, mortality registries, the mortality registries, the behaviour of not-lived- adoptive or step-parent
113,762 not-lived-with father, Suspicion and Crime registers, Suspicion and Crime with biological parents correlated with offspring drug
10,194 not-lived-with mother, drug-related driving offences, registers, drug-related were correlated with abuse (r range = 0.06–0.09)
65,803 stepfather, and the Prescribed Drug driving offences, and the offspring drug abuse (r
17,637 stepmother, 10,038 adoptive Register Prescribed Drug Register range = 0.13–0.19)
families
Age: not reported
Kendler Matched-pairs case–control Snr Drug abuse: medical registers, Drug abuse: medical Control parent–child pairs Not studied Yes, exposed offspring were at
et al.11 65,006 parent–offspring, sibling, the Crime Register, the registers, the Crime matched on sex, parent and increased risk of drug abuse
and cousin pairs Suspicion Register, and drug- Register, the Suspicion child year of birth, country of than matched control offspring
Age: 19–23 years related driving offences Register, and drug- birth, SES, number of lifetime who were unexposed to
related driving offences drug abuse registrations, parental drug registration
in offspring whose medical or criminal
parents had a drug registration, parental EA
abuse incident 1–3
years ago
Kendler Multiple parenting Snr Drug abuse: medical registries, Drug abuse: medical Drug abuse or AUD status of Yes, drug abuse and Yes, drug abuse or AUD
et al.9 relationships design 475,000 parent–offspring pairs the Crime Register, the registries, the Crime all other relevant biological AUD registration of not- registration of adoptive or step-
Age: 15 and over Suspicion Register, drug- Register, the Suspicion and step-parents, offspring lived-with biological parent correlated with offspring
related driving offences, and Register, drug-related year of birth, and offspring sex parents were correlated drug abuse or AUD (r range =
the Prescribed Drug Register driving offences, and the with offspring drug 0.04–0.10)
AUDs: medical and mortality Prescribed Drug Register abuse and AUD (r range
registries, the Suspicion AUDs: medical and = 0.14–0.16)
Register, the Crime Register, mortality registries, the
and the Prescribed Drug Suspicion Register, the
Register Crime Register, and the
Prescribed Drug Register
Page 31 of 38
Table 6 continued
Kendler Extended family design Snr Drug abuse and alcohol use Drug abuse: medical Child sex, year of birth Not studied Yes, after accounting for genetic
et al.102 44,250 children of high-risk parents disorder: medical registries, the registers, the Crime relatedness, parent (and step-
(affected with drug abuse), and Crime Register, the Suspicion Register, the Suspicion parent) drug abuse, AUD,
offspring of discordant sibling or Register, drug-related driving Register, drug-related criminal behaviour and
sibling-in-law offences, and the Prescribed driving offences, and the psychiatric registration was
Age: 15 and over Drug Register Prescribed Drug Register associated with offspring
Criminal behaviour: Swedish drug abuse
Crime register
Psychiatric registration: any
mental disorder
Cea & Adoption VFS Parenting styles: offspring Polysubstance use: self- Age, gender, and Not studied At T1, adoptive family cohesion,
Barnes108 328 biological and 77 adoption report, family cohesion report, composite score, adoption status parental monitoring, maternal
families (FACES-II), mother & father alcohol composition and paternal positive parenting,
Age: 14–33 years care, mother & father (Volume-Variability and father overprotection were
overprotectiveness (PPBI), Index), smoking, and associated with offspring
parental monitoring, mother other drug usage at time substance use (maternal and
and father support, mother and 1 (T1: 14–25 years) and paternal coercion, maternal
father control (GBF) T2 (21–33 years) overprotectiveness coercion
were not). At T2, only cohesion,
maternal coercion and
overprotection were significant
Cea & Adoption VFS Addiction-prone personality: Addiction-prone Adoption status, and Not studied Adoptive parent addiction-
Barnes104 328 biological and 77 adoption self-report, APP-21 personality: self-report, child gender prone personality and familial
families Familial care factor: mother, APP-21 care factor were associated with
Age: 14–33 years father & offspring report, PPBI offspring addiction-prone
and FACES-II personality
Samek Adoption SIBS Parental involvement: offspring Substance use: self- Earlier substance use Not studied Yes, adoptive parental No evidence of passive
et al.107 568 adopted and 412 biological report, an average of the report, CSUA involvement was negatively rGE found
offspring maternal and paternal associated with offspring
Age: 11–25.5 years score, PEQ substance use
Kendler Sibling comparison Snr Adoptive parenting: protective Drug abuse: medical Parental age at birth, high-risk Not studied Children exposed to adoptive
et al.109 1161 full sibships and 3085 half- effect of high-quality rearing registers, the Suspicion status of the other parent of parenting had a lower risk of
sibships of high-risk biological environment Register, the Crime half-sibling, child gender drug abuse than their
parents; one sibling reared by Register, drug-related unexposed siblings, this
biological, other by adoptive driving offences, and the protective effect disappeared
parents Prescribed Drug Register when the adoptive family was
Age: 15 and over disrupted or if there was a high-
risk adoptive parent
G–E gene–environment, G×E gene–environment interaction, rGE gene–environment correlation.

Design = PGS Polygenic scores.
Samples = A-25 Australia 25,000 study, MATCH Mothers and Their Children Study, MO-MATCH Missouri Mothers and Their Children Study, PACER Parent Alcoholism and Child Environmental Risk Study, SIBS Sibling Interaction
and Behaviour Study, Snr Swedish National Registers, VET Vietnam Era Twin Registry, VFS Vancouver Family Survey, V-30 Virginia 30,000 study.
Measures = APP-21 Addiction-Prone Personality-21 Scale, CSUA Computerised Substance Use Assessment, DIS Diagnostic Interview Schedule, DUSI revised Drug Use Screening Inventory, FACES-II Family Adaptability and
Cohesion Evaluation Scales II, GBF Grace Barnes and Farrell’s 1982 Study, MAGIC-PC Missouri Assessment of Genetics Interview for Children–Parent on Child, PEQ Parental Environment Questionnaire, PPBI Parker Parenting
Bonding Instrument, SAGA Semi-structured Assessment of the Genetics of Alcoholism.
Statistics = OR odds ratio, HR hazard ratio, r weighted tetrachoric correlation. Effect sizes are not reported for studies that did not investigate both genetic and environmental transmission.
Page 32 of 38
Parenting behaviours with offspring internalising or externalising behaviours

Studies investigating the associations between parenting through environmental pathways. For maternal exposures,
behaviours and offspring substance use (Table 6) showed these associations were related to concurrent maternal
that adoptive parenting behaviours such as parental symptoms, with no long-lasting effect of prenatal depression
involvement107, family care104, family cohesion, parental or anxiety on offspring mental health. Other environmental
monitoring, parental care and parental support108 were associations and rGEs were observed for parent–offspring
associated with a lowered risk of offspring substance use similarity in criminal behaviours, substance use behaviours,
behaviours, whereas adoptive parents’ overprotectiveness and educational attainment. In addition, positive and nega-
or control had no effect108. In addition, children exposed tive parenting behaviours held associations with offspring
to adoptive parenting had a lower risk of drug abuse than internalising behaviours, externalising behaviours, substance
their unexposed sibling, indicating a protective effect of use behaviours, and educational attainment, with some
adoptive parenting on substance use behaviours, which evidence of rGE. Finally, cross-lagged studies showed
was also reported for MDD above109. bidirectional associations between parenting traits and off-
spring behaviours, where parenting predicted offspring
Offspring personality behaviours, and offspring behaviours predicted parenting.
There was evidence of genetic and environmental The reviewed literature highlights that genetically
influences underlying associations between parental informative designs must be implemented to model or
characteristics and offspring personality (Table 7). Parent control for genetic effects in studies investigating parental
sociability and offspring positive emotionality110, and influences on offspring development. There was sub-
parent behavioural motivation and offspring social moti- stantial evidence of genetic overlap between parental and
vation61 shared common genetic factors, whereas the offspring phenotypes for both similar traits (e.g. parental
intergenerational transmission of neuroticism seemed to depression and offspring internalising symptoms)19–23
be environmentally explained29. There was no evidence of and dissimilar traits (e.g. parental depression and off-
an environmental association between parental traits, spring externalising problems)19–22,56. As well as indicat-
including anxiety111, sociability110, and smoking during ing genetic transmission of similar traits, these findings
pregnancy71, and offspring personality traits such as indicate that the same genetic factors may be relevant for
sociability and temperament. In addition, an extended the development of several distinct mental health pro-
twin study found no evidence of environmental trans- blems92, and could also partly explain the comorbidity
mission or rGE underlying associations between parent between mental health disorders that is widely observed
and offspring dimensional personality traits112. However, in literature113. Without accounting for genetic trans-
two studies observed evocative effects of offspring social mission within families, observational studies run a ser-
behaviours on parenting; adopted offspring’s genetically ious risk of misinterpreting these associations as causal
influenced social behaviours predicted adoptive parent environmental influences. For instance, it was observed
hostility61 and child-centred parenting111. Overall, current that after accounting for shared genetic effects, perinatal
and previous literature indicates that relationships maternal depression did not hold any long-lasting asso-
between parental factors and offspring personality vary ciations with offspring internalising or externalising
substantially by phenotype, and can involve both genetic behaviours in childhood21,22,24,31,34. This is in contrast to
and environmental processes. the substantial body of literature that interprets associa-
tions between perinatal maternal distress and offspring
Discussion mental health outcomes in causal terms35. We urge future
This review provides a broad overview of genetically studies investigating parent–offspring associations to err
informative literature investigating associations between on the side of caution in interpreting their results and
parental characteristics and offspring mental health and consider evidence from multiple methodologies in form-
related outcomes. This is a topic of substantial interest, with ing their conclusions. Even genetically informative designs
89 relevant articles published in the past 6 years. Overall, can be skewed towards non-genetic findings if there is
reviewed studies showed reliable evidence of genetic trans- insufficient power in the study. Triangulating evidence
mission of depression, criminal behaviour, educational from multiple methodologies is required before a general
attainment, and substance use behaviours from parent-to- conclusion can be reached on whether a given
child. Additionally, cross-phenotype genetic overlap was parent–offspring association is likely to be truly present,
observed in several instances; for example, parental depres- after accounting for shared genetic effects or rGE.
sion, substance use, and educational attainment were all Even so, the reviewed studies indicate that both genetic
associated with offspring externalising behaviours through and environmental factors are important in associations
genetic pathways (Table 2). After accounting for genetic between parental factors and offspring mental health out-
transmission, parental depression or anxiety were associated comes (Table 2). These overall findings raise two important
Table 7 Detailed characteristics of studies investigating offspring personality (N = 6).
Offspring personality
Study Design Sample Parental attribute (predictor) Child attribute (outcome) Control variables Genetic overlap Environmental G–E interplay
transmission
Elam et al.61 Adoption EGDS Adoptive parent hostility: self- Toddler low social motivation: Prenatal risk and Yes, birth mother low Yes, adoptive parent Evocative rGE: birth
316 families report, IFIRS observation & parent report, obstetric complications, behavioural motivation hostility predicted mother low behavioural
Age: 27 months Birth mother low behavioural composite score and adoption openness predicted toddler low offspring disruptive peer motivation predicted
to 4.5 years motivation: self-report, BIBA social motivation (β = behaviour (β = 0.11–0.28) toddler low social
0.17) motivation, which
predicted adoptive
parent–child hostility
Ellingson Sibling CNLSY Smoking during pregnancy: self- Temperament/personality: Maternal age at birth, EA, Not studied No difference in
et al.71 comparison 10,251 children report, mean number of packs maternal report, CBQ intelligence, temperament/personality
of 4,827 mothers smoked per day, reported after delinquency, offspring between exposed and
Age: 4–14 years pregnancy sex, birth order, ethnicity, unexposed siblings
household income,
geographic location
Van Ryzin Adoption EGDS Responsive parenting: Social competence: parent and Openness/contact in the Birth-parent sociability Adoptive responsive G×E: birth parent
et al.110 361 families observation & self-report, teacher-report, composite adoption, prenatal risk predicted offspring parenting did not predict sociability x adoptive
Age: 9 months to composite score, HOME score, SSRS and SCSA index, child positive social competence, (β = offspring social parent responsive
6 years Birth parent sociability: parental emotionality at 0.17) but this association competence parenting: offspring
self-report, composite 9 months did not remain after social competence
score, ATQ adjusting for child
positive emotionality
Eley et al.29 Children-of-twins TOSS Neuroticism: self-report, EPQ Neuroticism: self-report, EPQ Twin sex, and age No shared genetic Yes, after accounting for
387 MZ, 489 DZ effects between parental genetic relatedness,
families and offspring parental neuroticism was
Age: 11–22 neuroticism associated with offspring
neuroticism (effect size
not clear)
Brooker Adoption EGDS Child-centred parenting: Social inhibition: observation, Prenatal risk and No, birth parent anxiety No, adoptive parent–child- Evocative rGE: birth
et al.111 505 families observation, three independent coders obstetric complications, did not predict offspring centred parenting or parent anxiety and child
Age: independent coders adoption openness, social inhibition anxiety did not predict social inhibition
9–18 months Adoptive and birth parent adoptive parent EA, and offspring social inhibition predicted adoptive
anxiety symptoms: self- child sex mother–child-centred
report, BAI parenting
G×E: birth parent anxiety
x adoptive father–child-
centred parenting: social
inhibition
Kandler Extended twin SPAD Personality dimensions: self- Personality dimensions: self- Age, sex Not studied No, maternal or paternal No evidence of passive
et al.112 573 twins and report, HEXACO, six dimensions: report, HEXACO, six dimensions: shared environment rGE found
their families honesty–humility, emotionality, honesty–humility, emotionality, effects were not
Mean age: extraversion, agreeableness, extraversion, agreeableness, associated with offspring
~39 years conscientiousness, openness conscientiousness, openness personality

Samples = CNLSY Children of the National Longitudinal Survey of Youth, EGDS Early Growth and Development Study, SPAD Study of Personality Architecture and Dynamics, TOSS Twin Offspring Study of Sweden.
Measures = ATQ Adult Temperament Questionnaire, BAI Beck Anxiety Inventory, BIBA Behavioural Inhibition/Behavioural Activation scales, CBQ Children’s Behaviour Questionnaire, EPQ Eysenck Personality Questionnaire,
HEXACO HEXACO Personality Inventory-Revised, HOME Home Observation for Measurement of the Environment, IFIRS Iowa Family Interaction Rating Scales, SSRS Social Skills Rating System, SCSA Social Competence and
School Adjustment.
Statistics = β standardised parameter estimate. Effect sizes are not reported for studies that did not investigate both genetic and environmental transmission.
Page 34 of 38
questions; to what extent are parent–offspring associations evocative rGE effects were not observed, child-to-parent
due to genetic transmission, and to what extent does par- effects were sometimes still present19,28,30,32,36,65. These
enting truly matter? Findings from classical twin literature findings highlight the bidirectional and dynamic nature of
indicate that between 40 and 80% of individual differences in parent–offspring associations, with child-to-parent effects, as
mental health phenotypes such as internalising and exter- well as parent-to-child effects, and also show the importance
nalising problems between people are explained by additive of cross-lagged models in modelling parent–offspring asso-
genetic effects3. This suggests that the largest way through ciations over time.
which parents influence offspring mental health outcomes is Reviewed findings with clinical implications are worth
through the passing on of their genes. In addition, estimates highlighting further. Parents with depression, anxiety, sub-
of heritability for mental health phenotypes within classical stance use problems, and externalising behaviours appeared
twin literature tend to increase with age, while the influence to pass on these traits to the offspring through both genetic
of the shared family environment decreases114. From a and environmental mechanisms. This information can be
developmental perspective, this indicates that genetic influ- used to extend preventative and early intervention services
ences on offspring mental health become increasingly to high-risk children of parents with internalising, exter-
important as the child gets older while the overall environ- nalising, or substance use disorders in healthcare settings.
mental impact of parental characteristics on offspring Family-based interventions, including cognitive, beha-
behaviour is likely to be small. In the current review, effect vioural, and psychoeducational components, are already
sizes showing the relative contribution of genetic and shown to be effective in children of parents with inter-
environmental factors in parent–offspring associations were nalising and externalising disorders120. In addition, several
not consistently reported and the available statistics are hard reviewed studies showed that positive parental environ-
to compare between studies. Some studies reported higher ments, such as parental warmth and positive reinforcement,
effect sizes for genetic or environmental transmission, while were protective against externalising and substance use
others reported equal effect sizes for genetic and environ- behaviours in children with high inherited risk51,52,109.
mental effects in parent–offspring associations (Tables 3–7). Whilst preventative interventions for externalising pro-
Based on prior knowledge, the overall effect of any single blems already include a family component, current pre-
parental environmental exposure is likely to be far lower ventative strategies for substance use incorporate school-
than the estimated heritability of offspring mental health and based and skills training approaches121. A family-based
related traits, as is the effect of a single genetic variant. It is approach could be a valuable addition to preventative
also worth highlighting that environmentally mediated interventions of substance use behaviours in early life.
influences can still be under the influence of parental genes. To conclude, parental factors are important predictors of
Previous twin literature shows that parenting behaviours are offspring mental health and related outcomes. Both genetic
under genetic influence themselves and reflect heritable and environmental processes are important in these asso-
individual differences115–117. Genetic nurture is a new way to ciations. Further clarification of these processes requires
index the environmentally mediated effect of parental genes more research. Exciting opportunities for parent–offspring
on offspring behaviour. The reviewed studies provide evi- research are increasingly present, with the availability of
dence of genetic nurture effects on offspring internalising more datasets and ongoing advances in methodologies.
symptoms and educational attainment (Table 2). This is a
promising area of research and we expect the development
Acknowledgements
and application of genetic nurture designs to continue to This work was supported by the European Union’s Horizon 2020 research and
expand in the coming years. innovation programme, Marie Sklodowska Curie Actions—MSCA-ITN-2016—
As well as demonstrating genetic overlap and environ- Innovative Training Networks (grant number 721567; CAPICE project). Eshim S.
Jami was supported by an Academy Ter Meulen grant from the Royal
mental transmission within parent–offspring associations, Netherlands Academy of Arts and Sciences, and Anke R. Hammerschlag was
the reviewed studies showed that confounding by passive supported by the Children’s Hospital Foundation and University of Queensland
rGE is also prevalent within genetically informative designs strategic funding. Meike Bartels is supported by a European Research Council
consolidator grant (grant number 771067 WELL-BEING). The authors thank
(Table 2). If unmodelled, these unmeasured effects may Zainab Humayun for the illustrations used in Figs. 1 and 2.
inflate the estimation of both genetic and environmental
factors. Additionally, evocative rGE can also explain
parent–offspring associations. The reviewed studies showed Author details
1
evidence of evocative rGEs underlying associations between Department of Biological Psychology, Vrije Universiteit Amsterdam,
Amsterdam, the Netherlands. 2Department of Clinical, Educational and Health
parental characteristics and offspring internalising symptoms, Psychology, Division of Psychology and Language Sciences, University College
externalising symptoms and personality (Table 2). These London, London, UK. 3Amsterdam Public Health Research Institute, Amsterdam
findings are compatible with previous literature which shows University Medical Centres, Amsterdam, the Netherlands. 4Child Health
Research Centre, University of Queensland, Brisbane, QLD, Australia. 5Child and
a moderate impact of offspring’s genetically influenced Youth Mental Health Service, Children’s Health Queensland Hospital and
behaviours on parenting factors118,119. In instances where Health Service, Brisbane, QLD, Australia
Conflict of interest 22. Gjerde, L. C. et al. Associations between maternal depressive symptoms and
The authors declare no competing interests. risk for offspring early-life psychopathology: the role of genetic and non-
genetic mechanisms. Psychol. Med. 1–9 (2019).
Publisher’s note 23. Kendler, K. S., Ohlsson, H., Sundquist, K. & Sundquist, J. Sources of parent-
Springer Nature remains neutral with regard to jurisdictional claims in offspring resemblance for major depression in a national Swedish extended
published maps and institutional affiliations. adoption study. Jama Psychiatry 75, 194–200 (2018).
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Received: 3 April 2020 Revised: 19 February 2021 Accepted: 3 March 2021
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Jami et al.

Translational Psychiatry (2021)11:197

REVIEW ARTICLE Open Access

Parental characteristics and offspring mental health

Introduction Thus, observed parent–offspring associations may be wholly

© The Author(s) 2021

Behavioural genetics designs

impact of other family

to account for shared parent–child genetic

SNP-based heritability - Datasets with parent–offspring

Molecular genetics designs only a part of the overall parent-to-child environmental

Results Offspring internalising behaviours

Offspring internalising behaviours

Offspring educational attainment

siblings, but perinatal

behaviour (effect behaviour effect size

children-of-twins and anxiety symptoms, and

G–E gene–environment, G × E gene–environment interaction, rGE gene–environment correlation.

Parental anxiety or depression

composite score, criminal

(R2 = 14.2–29.3%) (R2 = 0.4–1.3%)

offspring criminality (effect size for genetic relatedness,

G–E gene–environment, G×E gene–environment interaction, rGE gene–environment correlation.

PGS was not associated

child PGS (HRS sample; from β = 0.314

parents’ age, type of

G–E gene–environment, G × E gene–environment interaction, rGE gene–environment correlation.

Age: up to 20 years or drug-related maternal smoking siblings, and after accounting

G–E gene–environment, G×E gene–environment interaction, rGE gene–environment correlation.

Parenting behaviours with offspring internalising or externalising behaviours

G–E gene–environment, G × E gene–environment interaction, rGE gene–environment correlation.

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