9

The “discovery” of the “gay gene”

In 1993, the West was told that a scientist had discovered a “gay gene”—a
gene causing homosexuality. The details were confusing for non-scien-
tists, but the headline stuck. For Mr and Ms Average Citizen, it seemed
that homosexuality might be genetic.
Actually there was no “gay gene.” Even the scientist referred to, a
gay man, Dean Hamer of the United States National Institutes of Health,
never claimed to have found a gene determining homosexuality. “We
have not found the gene—which we don’t think exists— for sexual orien-
tation,” he said.1 However, he claimed to have found evidence that some
male homosexuality was passed through female members of a family.
More specifically, he claimed to have found a linkage between homosex-
uality in males and a small stretch of the DNA on the X -chromosome.2
This chapter will look at these studies, but as discussed in Chapters
One and Eight, scientists now believe that thousands of genes may be
involved in almost any trait and that gene expression depends on envi-
ronmental events and even social interactions. Gene patterns may be a
recipe for tissues and bodies, but don’t dictate behaviours. Though much
research has tried to find specific SSA genes, none have yet been conclu-
sively found. Any connections are very weak, indirect, not specifically

145
146 MY GENES MADE ME DO IT

sexual and we’ll see that a very large 2019 study shows an alarming
amount of early work was simply wrong.

Gene linkage studies

Hamer’s work falls into a category of research called “gene linkage stud-
ies.” There was a surge of research in this field in the late twentieth
century but because thorough “whole genome” scans are now the norm,
gene linkage studies are becoming rather passé. A whole genome scan
means all the genes are examined; a gene linkage can only look at a few
at a time.
The first most spectacular linkage study, was the discovery, early
in 1993, of a gene responsible for Huntington’s disease. The gene had
already been tracked down to chromosome 4, but it took six teams of
workers at ten different institutions ten years to find whereabouts on
chromosome 4. Over the succeeding decade, researchers also identified
genes causing cystic fibrosis, muscular dystrophy, and other diseases.
From 1990 to 1993 biologists had astonishing success mapping the
human genome (on schedule and within budget!) and analyses are still
being published. In one five year period near the end of the nineties,
the genes corresponding to 1450 physical conditions were identified
and their precise location on various chromosomes found. Inspired by
these successes, some scientists began talking optimistically of uncov-
ering the genetic basis to human behaviours in the same way. This is
what Hamer tried to do, and what other scientists, called behavioural
geneticists, had attempted to do before him, but with scant success.

What happens in Gene Linkage studies?

In linkage studies for behaviour, researchers look for an extended family
with an unusually high incidence of some behaviour, such as bipolar
disorder, and then take samples of tissue from all available members
and analyse the DNA, looking for segments in common using sets of
tiny, synthesised DNA segments, called “markers”—an identical set for
each person. These tiny markers are configured in such a way that they
attach in a lock and key fashion to any stretches of DNA that mirror the
markers; they usually contain a small range of genes. Searching for one
gene in 22,000 is worse than looking for a contact lens in a swimming
pool, but, in this way, segments of DNA (also containing “irrelevant”
 The “discovery” of the “gay gene”147

genes) can be found in different people. If the same sequence is associ-

ated consistently with a given trait, then researchers assume the marker
lies close to the gene that codes for it, along with the other irrelevant
genes. At that point, the researchers believe they have found a linkage.
The strength of linkage analysis is in studying physical diseases
that have distinct symptoms and are caused by a single dominant gene.
When they attempt to link behaviours to a single gene, they run into a
volley of scientific scepticism, for several reasons.
First, no mainstream geneticist believes that behaviour is linked
to one single gene (see Chapter One). “It’s very rare to find genes that
have a specific effect,” says Harvard biologist Balaban.3 Second, in the
word of one writer for Science, “the field of behavioural genetics is
littered with apparent [gene linkage] discoveries that were later called
into question or retracted.”4 It was only in the first decade of the 21st
century that gene linkage studies became more reliable. Unfortunately
the supposed SSA—genetic link was publicised before that time. And,
as mentioned, the most recent studies have moved beyond linkage stud-
ies to very detailed scans of the entire genome.
In the next section we survey gene linkage studies that have tried
to identify genes linked to schizophrenia, to put in perspective what is
needed for success in gene linkage studies.
About the time Hamer sought to associate SSA with a section of the
X-chromosome, linkage studies were scientifically dubious, but seemed
worth pursuing although similar gene linkage studies on schizophrenia
and alcoholism had given rather contradictory results.

Schizophrenia
Gene linkage studies on schizophrenia blossomed with the comple-
tion of the human genome project. Using markers, many regions were
found on various chromosomes which correlated strongly with schiz-
ophrenia, and studies on fresh family lineages and families from other
ethnicities often confirmed them, though there were puzzling lacks of
confirmation from time to time.
However the results for some regions of the DNA seemed so
convincing that scientists began looking for specific genes within them.
By August 2005, at least 25 chromosome regions were thought to be
involved, and an equal number of genes on them were being investigated.
148 MY GENES MADE ME DO IT

Of these there was strong evidence for involvement of 4 genes and

“promising but not compelling evidence” for a fifth. Some of the results
were described as “very robust.” This was a good consensus to emerge
from a welter of initially inconsistent gene linkage studies. The work had
progressed so far that some researchers started to experiment with drugs
which interacted with the products of the genes known to be involved, in
the hope of reversing or at least reducing the progress of schizophrenia.
But this confidence proved to be completely ill-founded. By
mid-2010 “whole genome” scanning had thrown the gene linkage results
into embarrassing disarray. In “whole genome” scanning—rather than
using markers which result in rough screening only—all the genes are
scanned in extraordinary detail, nucleotide by nucleotide. Nucleotides
are subunits of DNA There are hundreds of nucleotides in a single gene,
each made up of a nitrogen base, a sugar and phosphate.
Enormous multicenter efforts scanned the entire genomes of 7662
subjects and 29053 controls in one study alone; a second involved 3322
subjects and 3587 controls, and a third involved 8008 subjects and 19077
controls but altogether they could not confirm any of the previous
gene-linkage work, only labelling them promising. The detailed saga is
recounted elsewhere.5 This was embarrassing because so much previous
work now seemed premature. One million gene variants were examined,
involving most common variations of DNA nucleotides. They found
absolutely unequivocal evidence of a connection to variants in a gene
on chromosome 6 linked to immunity, and to three other completely
new genes, two called transcription factors (TCF4 and ZNF804A, the
latter a “zinc finger” protein because of its composition and shape) and
the last, called neurogrannin, but, disconcertingly, noone had previ-
ously suspected them of being involved. The transcription factors were
used by the nucleus to read the DNA sequence and neurogranin is a
brain-specific protein connected with biochemical control of calcium.
Like the fruit-fly case we described in Chapter One, why these genes
should be important in schizophrenia is not at all obvious, and links
will be very indirect.
Schizophrenia is certainly reliant on multiple genes, because four
genes were found and others suspected: but these significant genes found
only account for 3% of schizophrenia. The effect is weak. This is a vivid
illustration of how difficult this field is.
 The “discovery” of the “gay gene”149

Hamer’s Study—SSA
Compared with the scale and outcomes of the schizophrenia project
above, early efforts which attempted to link genes with SSA now seem
embarrassingly small, very naive and hyper-optimistic. Moreover,
Chapter Ten shows the genetic contribution to SSA calculated another
way is relatively low, lowering the prospects of success from gene studies.
However: To find the homosexual gene or genes, Hamer and his
colleagues2 first recruited 76 men, who identified themselves as predom-
inantly or exclusively homosexual. They found 13.5% of their brothers
to be gay, much higher than the 1% occurrence of exclusive homosex-
uality in the general male population, and also found a higher level of
homosexuality in maternal uncles and the sons of maternal aunts. They
then recruited 38 families in which there were two homosexual broth-
ers, suspecting this would show more clearly the effect of homosexual-
ity and Hamer searched for a linkage on the X (female) chromosome.2
Hamer claimed to have found a “statistically significant correlation”
between the homosexual orientation and a genetic sequence on the tip
of the long arm of the X chromosome, an area called “Xq28”. Hamer
published his paper in Science, in July 1993, and immediately became
a controversial figure in the scientific community. Numerous letters to
the journal Nature were mostly critical.
In the meantime, Hamer11 and colleagues replicated their study
using a new population. This time, the results were less impressive—
only just statistically significant, but the replication was promising and
reassuring.
Hamer’s study on the “gay gene” was then contradicted in a gene
linkage study12 published in Western Ontario, headed by researcher
Rice. Rice found no trace of an association between homosexuality and
the genetic region Hamer and his team had pin-pointed. Even when the
results from all the Hamer and Rice studies were combined, there was
no significant association. Hamer argued that the Rice team result was
inadequate because they did not select homosexual men with an excess
of maternal homosexuality.
Then a “whole genome” study13 appeared from the National
Institutes of Health in Maryland, with collaborators from several parts
of the US. It was much larger than any preceding gene linkage study.
150 MY GENES MADE ME DO IT

The first author was called Mustanski, and Hamer was included in the
author list, though not leading the study.
According to the results in the paper, no part of the entire genome
was statistically significantly linked with SSA. One peak on Chromosome
7 (region 7q36) approached statistical significance but the result did not
survive replication by a 2014 study.
Then, using a different method, the Rice team10 could not replicate
the Mustanski results. So, more conflict!
In mid 2014 a Chicago researcher called Sanders headed a team
which published8 the result of investigating the genetic links yet again,
working on a sample of 409 SSA brothers. They found more convinc-
ing confirmation of the Xq28 linkage, but only suggested specific genes
which might be involved. Their comment is worth citing, “We also
emphasize that genetic contributions are far from determinant but
instead represent a part of the trait’s multifactorial causation both genetic
and environmental.” Translation: genes as a whole are a minor contri-
bution; there are many factors involved.
Much earlier Hamer’s group attempted an SSA-gene linkage study
on lesbians but did not find a link between parts of the X-chromosome
and the presence of lesbianism in families.
A 2015 Chinese study showed a connection between a gene called
COMT and sexual orientation,7 but calculation shows the effect size is
weak.

The large 2019 genome/SSA study

In 2019 the results of a very large study appeared in Science,14 one of the
top scientific journals, which claimed discovery of five genes connected
to SSA. They paid careful attention to statistical validity and the gene
discovery is probably correct, but their definition of SSA is surprisingly
poor, and the connection doesn’t mean very much. Perhaps they will
publish better material in future.
Where can you get the tens of thousands people needed for such
a gene/SSA study? Today it comes from places many readers will have
patronised—the half dozen companies analysing DNA for private clients.
Most results came from the UK Biobank company; nearly 409,000 volun-
teers had agreed to a survey on sexual matters. Results added in from
 The “discovery” of the “gay gene”151

other related companies and surveys increased this to 477,000—nearly

half a million. We’ll call this the Biobank study.
More than twenty authors are listed: from the USA, Sweden,
Denmark, Netherlands, UK, Australia and a combined research group
from the USA 23-and-Me genome company. This is Big Science.
The most serious problem is that researchers divided the group into
two classes: those who never had a same-sex partner, and those who had
at least one. Previous surveys describe this as a mediocre classification.
Even Kinsey in the late 1940’s talked about those who had merely
incidental SSA experience: one or two experiences and nothing there-
after. That’s the present case. Researchers know very well that many of
these sorts of encounters are exploratory or even sexual abuse, and not
a continuing sexual orientation. In fact, in this study, they comprise
most of those with some same-sex attraction. Laumann et al. (Chapter
Two) found 7% of men had reported one or more same-sex partners
but those active at the time of his survey were only 2.9% and exclusive
SSA men were about 1%. Most had not persevered. In the same way
Laumann et al. found 4% of women had one or more same-sex part-
ners, but those active at survey time were only 1.8%. This means the
Biobank study is mostly about sexual explorers. It’s dubious practice to
label them all “homosexual”.
The researchers warned there were two qualitatively different classes
of people­—those slightly non-heterosexual, and those exclusively homo-
sexual. The volunteers overall have a rather weak same-sex drive. Why
didn’t researchers concentrate on those with a strong drive? Well, that
would probably have reduced their sample size by a factor of 10, which
would make the results much less clear. So they faced a trade-off between
mediocre sample description or mediocre statistical test power.
“Getting your DNA done” is quite popular and perhaps the survey
will be repeated when there are ten times as many people available and
a large active SSA group, but let’s see what was possible even with the
available sample and doubtful sexual classification.
The researchers present the Biobank results first, and for men they
found a connection between four genes and some SSA experience.
Embarrassingly, these genes had never been implicated in nearly a dozen
similar preceding studies probably involving several million dollars of
effort. All the previous work was useless because samples were too small,
152 MY GENES MADE ME DO IT

but this was realised clearly only in the last five years or so. Even more
embarrassingly, the controversy about the genes on the X-chromosome,
particularly the XQ28 region was pointless—none of the four genes
Biobank researchers found were on the X-chromosome.
For the very first time researchers found three genes correlated
with SSA in women, and two of these were also found in men. No previ-
ous work had found any gene connections for women. There was some
overlap then, between genes for men and women and SSA, but over-
lap between men and women for most unrelated traits in other studies
was much higher. Could SSA be partly different in men and women?
Quite reasonable.
When the researchers checked the results using much smaller
samples from other sources, and a total of 15000 individuals, they
confirmed three of the results, which is a good test of reliability, but
the Biobank large sample results were far more reliable.
Two of the genes were connected to smell sensors. Could this be
SSA related? But previous studies could also point to vague connections
between their spurious genes and various functions and were wrong. So
even present alleged connections should be treated rather sceptically.
At this point you may be thinking, “Well, there may not be one
unique gene, but a handful. OK, so a small cluster of genes are respon-
sible for SSA? And they have a powerful effect?”
No, they don’t! The researchers were able to calculate the strength
of any effect, and an individual with one of the four genes is at most
0.4% more likely to be SSA. Yes, almost negligible. But it is typical of
what gene researchers find, which is why they conclude that many,
many genes influence traits, each with a very small effect strength. For
the Biobank study, the researchers were able to show that the minute
influences were spread fairly evenly among all the chromosomes, again
confirming there were very many genes and on all the chromosomes.
But what was the sum of all these many small influences? The
researchers were able to calculate a range depending on various assump-
tions and it was 8-25%. In the paper they imply a typical estimate of
the total influence strength would be 10%—as derived elsewhere in
this book. If 0% is no influence, and 100% is a dictatorship, then 50%
would be a medium influence, but 10% is quite weak—and obviously
quite indirect.
 The “discovery” of the “gay gene”153

If there was a strong physical effect on SSA, you’d expect special

genes concentrated in parts of the body, maybe within the brain or in
the sex organs. The researchers tested individual tissues for other genes
suspected of some correlation with SSA but didn’t find it, in fact they
found very few correlations with other physical traits (an exception was
a finger length ratio in women).
The researchers identified openness to new experiences and risk
behaviour in their group of people who had at least one same sex
encounter in the last year—though this was not a genetic test. But it
again raises the issue of whether their study was of people with SSA or
of sexual explorers.
That could also account for the partial gene similarities (overlap)
between the men and women—i.e. the common factor is openness to
new experience.
So, the Biobank Study, though impressive in its reach and resources,
is limited in reaching conclusions about genetic effects on SSA.

Summary
The authors of the paper also strongly emphasise a DNA test for gayness
is not possible. The scientific community realises that “our genes do
not make us do it”. Hamer has always believed that. To give him the
last word: “There will never be a test that will say for certain whether
a child will be gay. We know that for certain.”9 This means as clearly as
anyone could state, that no-one is born gay.
Those who believe that homosexuality has psychological and soci-
ological explanations have no difficulty with the possibility of genetic
linkages to homosexuality. They would argue that any genetic link to a
physical characteristic that might heighten a person’s sense of gender
non-conformity (a strong known predictor of later homosexuality),
could be held to be a contributing factor to later homosexuality. In a boy
these might be, e.g. genes related to slightness of build or poor physi-
cal co-ordination (making a boy poor at sports). In a girl they might
be factors like atypical physical strength, shape, height, or weight, or a
more masculine finger-length ratio. Links? Yes, but weak and indirect.
154 MY GENES MADE ME DO IT

References
1. McKie R. 1993. The myth of the gay gene. The Press(30 July):9
2. Hamer DH, Hu S, Magnuson VL, Hu N, Pattatucci AML. 1993. A linkage between
DNA markers on the X-chromosome and male sexual orientation. Science 261:321-7
3. Horgan J. 1993. Eugenics revisited. Scientific American 268 (June):92-100
4. Pool R. 1993. Evidence for homosexuality gene. Science 261:291-2
5. Nieratschker V, Nothen MM, Rietschel M. 2010. New genetic findings in schizophrenia:
Is there still room for the dopamine hypothesis of schizophrenia? Frontiers in Behavioral
Neuroscience 4:23-32
6. Plomin R, Hill L, Craig IW, McGuffin P, Purcell S, Sham P, Lubinski D, Thompson
LA, Fisher PJ, Turic D, Owen MJ. 2001. A genome-wide scan of 1842 DNA markers
for allelic associations with general cognitive ability: a five-stage design using DNA
pooling and extreme selected groups. Behavior Genetics 31:489-95
7. Yu, W, Tu, D, Hong, F, Wang, J, Liu, X, Cai, Y, Shu, R, Zhao, G, Wang, F, Pan, H, Wu, S.
(2015) Analysis of the Association between Catechol-O-Methyltransferase Val158Met
and Male Sexual Orientation. Journal of Sexual Medicine, 12(9):1920-1926
8. Sanders, AR, Martin, ER, Beecham, GW, Guo, S, Dawood, K, Rieger, G, Badner, JA,
Gershon, ES, Krishnappa, RS, Kolundzija, AB, Duan, J, Gejman, PV, Bailey, M 2014.
Genome-wide scan demonstrates significant linkage for male sexual orientation.
Psychological Medicine 17:1-10
9. Holmes B. 1994. Gay gene test ‘inaccurate and immoral’. New Scientist 141 (5 March):9
10. Ramagopalan SV, Dyment DA, Handunnetthi L, Rice GP, Ebers GC. 2010. A genome-
wide scan of male sexual orientation. Journal of Human Genetics 55:131-132
11. Hu S, Pattatucci AML, Patterson C, Li L, Fulker DW, Cherny SS, Kruglyak L, Hamer
DL. 1995. Linkage between sexual orientation and chromosome Xq28 in male but not
in females. Nature Genetics 11:248-256
12. Rice G, Anderson C, Risch N, Eber G. 1999. Male homosexuality: absence of linkage to
microsatellite markers at Xq28. Science 284:665-7
13. Mustanski BS, DuPree MG, Nievergelt CM, Bocklandt S, Schork NJ, Hamer DH. 2005.
A genome-wide scan of male sexual orientation. Human Genetics 116:272-8
14. Ganna A, Verweij K, Nivard M, Maier R, Wedow R, Busch A, Abdellaoui A, Guo S,
Sathirapongsasuti J, Team 23andMe Research, et al. 2019. Large-scale GWAS reveals
insights into the genetic architecture of same-sex sexual behavior. Science (80- ).
365:eaat7693.