Genetically elevated high-density lipoprotein cholesterol through the cholesteryl ester transfer protein gene does not associate with risk of Alzheimer's disease
© 2018 The Authors 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.
Peloso, GM; van der Lee, SJ; Sims, R; 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
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