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Article
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Genetically elevated high‐density lipoprotein cholesterol through the cholesteryl ester transfer protein gene does not associate with risk of Alzheimer's disease

Peloso, Gina M;
van der Lee, Sven J;
Project, International Genomics of Alzheimer's;
Sims, R;
van der Lee, SJ;
Naj, AC;
Bellenguez, C;
Badarinarayan, N;
Jakobsdottir, J;
Kunkle, BW;
Boland, A;
Raybould, R;
Bis, JC;
Martin, ER;
Grenier‐Boley, B;
Heilmann‐Heimbach, S;
Chouraki, V;
Kuzma, AB;
Sleegers, K;
Vronskaya, M;
Ruiz, A;
Graham, RR;
Olaso, R;
Hoffmann, P;
Grove, ML;
Vardarajan, BN;
Hiltunen, M;
Nöthen, MM;
White, CC;
Hamilton‐Nelson, KL;
Epelbaum, J;
Maier, W;
Choi, SH;
Beecham, GW;
Dulary, C;
Herms, S;
Smith, AV;
Funk, CC;
Derbois;
Forstner, AJ;
Ahmad, S;
Li, H;
Bacq, D;
Harold, D;
Satizabal, CL;
Valladares, O;
Squassina, A;
Thomas, R;
Brody, JA;
Qu, L;
Sánchez‐Juan, P;
Morgan, T;
Wolters, FJ;
Zhao, Y;
Garcia, FS;
Denning, N;
Fornage, M;
Malamon, J;
Naranjo, MCD;
Majounie, E;
Mosley, TH;
Dombroski, B;
Wallon, D;
Lupton, MK;
Dupuis, J;
Whitehead, P;
Fratiglioni, L;
Medway, C;
Jian, X;
Mukherjee, S;
Keller, L;
Brown, K;
Lin, H;
Cantwell, LB;
Panza, F;
McGuinness, B;
Moreno‐Grau, S;
Burgess, JD;
Solfrizzi, V;
Proitsi, P;
Adams, HH;
Allen, M;
Seripa, D;
Pastor, P;
Cupples, LA;
Price, ND;
Hannequin, D;
Frank‐García, A;
Levy, D;
Chakrabarty, P;
Caffarra, P;
Giegling, I;
Beiser, AS;
Giedraitis, V;
Hampel, H;
Garcia, ME;
Wang, X;
Lannfelt, L;
Mecocci, P;
Eiriksdottir, G;
Crane, PK;
Pasquier, F;
Boccardi, V;
Henández, I;
Barber, RC;
Scherer, M;
Tarraga, L;
Adams, PM;
Leber, M;
Chen, Y;
Albert, MS;
Riedel‐Heller, S;
Emilsson, V;
Beekly, D;
Braae, A;
Schmidt, R;
Blacker, D;
Masullo, C;
Schmidt, H;
Doody, RS;
Spalletta, G;
Longstreth, WT;
Fairchild, TJ;
Bossù, P;
Lopez, OL;
Frosch, MP;
Sacchinelli, E;
Ghetti, B;
Yang, Q;
Huebinger, RM;
Jessen, F;
Li, S;
Kamboh, MI;
Morris, J;
Sotolongo‐Grau, O;
Katz, MJ;
Corcoran, C;
Dunstan, M;
Braddel, A;
Thomas, C;
Meggy, A;
Marshall, R;
Gerrish, A;
Chapman, J;
Aguilar, M;
Taylor, S;
Hill, M;
Fairén, MD;
Hodges, A;
Vellas, B;
Soininen, H;
Kloszewska, I;
Daniilidou, M;
Uphill, J;
Patel, Y;
Hughes, JT;
Lord, J;
Turton, J;
Hartmann, AM;
Cecchetti, R;
Fenoglio, C;
Serpente, M;
Arcaro, M;
Caltagirone, C;
Orfei, MD;
Ciaramella, A;
Pichler, S;
Mayhaus, M;
Gu, W;
Lleó, A;
Fortea, J;
Blesa, R;
Barber, IS;
Brookes, K;
Cupidi, C;
Maletta, RG;
Carrell, D;
Sorbi, S;
Moebus, S;
Urbano, M;
Pilotto, A;
Kornhuber, J;
Bosco, P;
Todd, S;
Craig, D;
Johnston, J;
Gill, M;
Lawlor, B;
Lynch, A;
Fox, NC;
Hardy, J;
Consortium, ARUK;
Albin, RL;
Apostolova, LG;
Arnold, SE;
Asthana, S;
Atwood, CS;
Baldwin, CT;
Barnes, LL;
Barral, S;
Beach, TG;
Becker, JT;
Bigio, EH;
Bird, TD;
Boeve, BF;
Bowen, JD;
Boxer, A;
Burke, JR;
Burns, JM;
Buxbaum, JD;
Cairns, NJ;
Cao, C;
Carlson, CS;
Carlsson, CM;
Carney, RM;
Carrasquillo, MM;
Carroll, SL;
Diaz, CC;
Chui, HC;
Clark, DG;
Cribbs, DH;
Crocco, EA;
DeCarli, C;
Dick, M;
Duara, R;
Evans, DA;
Faber, KM;
Fallon, KB;
Fardo, DW;
Farlow, MR;
Ferris, S;
Foroud, TM;
Galasko, DR;
Gearing, M;
Geschwind, DH;
Gilbert, JR;
Graff‐Radford, NR;
Green, RC;
Growdon, JH;
Hamilton, RL;
Harrell, LE;
Honig, LS;
Huentelman, MJ;
Hulette, CM;
Hyman, BT;
Jarvik, GP;
Abner, E;
Jin, LW;
Jun, G;
Karydas, A;
Kaye, JA;
Kim, R;
Kowall, NW;
Kramer, JH;
LaFerla, FM;
Lah, JJ;
Leverenz, JB;
Levey, AI;
Li, G;
Lieberman, AP;
Lunetta, KL;
Lyketsos, CG;
Marson, DC;
Martiniuk, F;
Mash, DC;
Masliah, E;
McCormick, WC;
McCurry, SM;
McDavid, AN;
McKee, AC;
Mesulam, M;
Miller, BL;
Miller, CA;
Miller, JW;
Morris, JC;
Murrell, JR;
Myers, AJ;
O'Bryant, S;
Olichney, JM;
Pankratz, VS;
Parisi, JE;
Paulson, HL;
Perry, W;
Peskind, E;
Pierce, A;
Poon, WW;
Potter, H;
Quinn, JF;
Raj, A;
Raskind, M;
Reisberg, B;
Reitz, C;
Ringman, JM;
Roberson, ED;
Rogaeva, E;
Rosen, HJ;
Rosenberg, RN;
Sager, MA;
Saykin, AJ;
Schneider, JA;
Schneider, LS;
Seeley, WW;
Smith, AG;
Sonnen, JA;
Spina, S;
Stern, RA;
Swerdlow, RH;
Tanzi, RE;
Thornton‐Wells, TA;
Trojanowski, JQ;
Troncoso, JC;
Van Deerlin, VM;
Van Eldik, LJ;
Vinters, HV;
Vonsattel, JP;
Weintraub, S;
Welsh‐Bohmer, KA;
Wilhelmsen, KC;
Williamson, J;
Wingo, TS;
Woltjer, RL;
Wright, CB;
Yu, CE;
Yu, L;
Garzia, F;
Golamaully, F;
Septier, G;
Engelborghs, S;
Vandenberghe, R;
De Deyn, PP;
Fernadez, CM;
Benito, YA;
Thonberg, H;
Forsell, C;
Lilius, L;
Kinhult‐Stählbom, A;
Kilander, L;
Brundin, R;
Concari, L;
Helisalmi, S;
Koivisto, AM;
Haapasalo, A;
Dermecourt, V;
Fievet, N;
Hanon, O;
Dufouil, C;
Brice, A;
Ritchie, K;
Dubois, B;
Himali, JJ;
Keene, CD;
Tschanz, J;
Fitzpatrick, AL;
Kukull, WA;
Norton, M;
Aspelund, T;
Larson, EB;
Munger, R;
Rotter, JI;
Lipton, RB;
Bullido, MJ;
Hofman, A;
Montine, TJ;
Coto, E;
Boerwinkle, E;
Petersen, RC;
Alvarez, V;
Rivadeneira, F;
Reiman, EM;
Gallo, M;
O'Donnell, CJ;
Reisch, JS;
Bruni, AC;
Royall, DR;
Dichgans, M;
Sano, M;
Galimberti, D;
St George‐Hyslop, P;
Scarpini, E;
Tsuang, DW;
Mancuso, M;
Bonuccelli, U;
Winslow, AR;
Daniele, A;
Wu, CK;
GERAD/PERADES, CHARGE;
Peters, O;
Nacmias, B;
Riemenschneider, M;
Heun, R;
Brayne, C;
Rubinsztein, DC;
Bras, J;
Guerreiro, R;
Al‐Chalabi, A;
Shaw, CE;
Collinge, J;
Mann, D;
Tsolaki, M;
Clarimón, J;
Sussams, R;
Lovestone, S;
O'Donovan, MC;
Owen, MJ;
Behrens, TW;
Mead, S;
Goate, AM;
Uitterlinden, AG;
Holmes, C;
Cruchaga, C;
Ingelsson, M;
Bennett, DA;
Powell, J;
Golde, TE;
Graff, C;
De Jager, PL;
Morgan, K;
Ertekin‐Taner, N;
Combarros, O;
Psaty, BM;
Passmore, P;
Younkin, SG;
Berr, C;
Gudnason, V;
Rujescu, D;
Dickson, DW;
Dartigues, JF;
DeStefano, AL;
Ortega‐Cubero, S;
Hakonarson, H;
Campion, D;
Boada, M;
Kauwe, JK;
Farrer, LA;
Van Broeckhoven, C;
Ikram, MA;
Jones, L;
Haines, JL;
Tzourio, C;
Launer, LJ;
Escott‐Price, V;
Mayeux, R;
Deleuze, JF;
Amin, N;
Holmans, PA;
Pericak‐Vance, MA;
Amouyel, P;
van Duijn, CM;
Ramirez, A;
Wang, LS;
Lambert, JC;
Seshadri, S;
Williams, J;
Schellenberg, GD;
Destefano, Anita L;
Seshardi, Sudha

UC San Francisco Previously Published Works (2018)

Introduction

There is conflicting evidence whether high-density lipoprotein cholesterol (HDL-C) is a risk factor for Alzheimer's disease (AD) and dementia. Genetic variation in the cholesteryl ester transfer protein (CETP) locus is associated with altered HDL-C. We aimed to assess AD risk by genetically predicted HDL-C.

Methods

Ten single nucleotide polymorphisms within the CETP locus predicting HDL-C were applied to the International Genomics of Alzheimer's Project (IGAP) exome chip stage 1 results in up 16,097 late onset AD cases and 18,077 cognitively normal elderly controls. We performed instrumental variables analysis using inverse variance weighting, weighted median, and MR-Egger.

Results

Based on 10 single nucleotide polymorphisms distinctly predicting HDL-C in the CETP locus, we found that HDL-C was not associated with risk of AD (P > .7).

Discussion

Our study does not support the role of HDL-C on risk of AD through HDL-C altered by CETP. This study does not rule out other mechanisms by which HDL-C affects risk of AD.

Cover page: Genetically elevated high‐density lipoprotein cholesterol through the cholesteryl ester transfer protein gene does not associate with risk of Alzheimer's disease