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.

Genetically elevated high-density lipoprotein cholesterol through the cholesteryl ester transfer protein gene does not associate with risk of Alzheimer's disease / G.M. Peloso, S.J. van der Lee, R. Sims, S.J. van der Lee, A.C. Naj, C. Bellenguez, N. Badarinarayan, J. Jakobsdottir, B.W. Kunkle, A. Boland, R. Raybould, J.C. Bis, E.R. Martin, B. Grenier-Boley, S. Heilmann-Heimbach, V. Chouraki, A.B. Kuzma, K. Sleegers, M. Vronskaya, A. Ruiz, R.R. Graham, R. Olaso, P. Hoffmann, M.L. Grove, B.N. Vardarajan, M. Hiltunen, M.M. Nöthen, C.C. White, K.L. Hamilton-Nelson, J. Epelbaum, W. Maier, S.H. Choi, G.W. Beecham, C. Dulary, S. Herms, A.V. Smith, C.C. Funk, N. Derbois, A.J. Forstner, S. Ahmad, H. Li, D. Bacq, D. Harold, C.L. Satizabal, O. Valladares, A. Squassina, R. Thomas, J.A. Brody, L. Qu, P. Sánchez-Juan, T. Morgan, F.J. Wolters, Y. Zhao, F.S. Garcia, N. Denning, M. Fornage, J. Malamon, M.C.D. Naranjo, E. Majounie, T.H. Mosley, B. Dombroski, D. Wallon, M.K. Lupton, J. Dupuis, P. Whitehead, L. Fratiglioni, C. Medway, X. Jian, S. Mukherjee, L. Keller, K. Brown, H. Lin, L.B. Cantwell, F. Panza, B. Mcguinness, S. Moreno-Grau, J.D. Burgess, V. Solfrizzi, P. Proitsi, H.H. Adams, M. Allen, D. Seripa, P. Pastor, L.A. Cupples, N.D. Price, D. Hannequin, A. Frank-García, D. Levy, P. Chakrabarty, P. Caffarra, I. Giegling, A.S. Beiser, V. Giedraitis, H. Hampel, M.E. Garcia, X. Wang, L. Lannfelt, P. Mecocci, G. Eiriksdottir, P.K. Crane, F. Pasquier, V. Boccardi, I. Henández, R.C. Barber, M. Scherer, L. Tarraga, P.M. Adams, M. Leber, Y. Chen, M.S. Albert, S. Riedel-Heller, V. Emilsson, D. Beekly, A. Braae, R. Schmidt, D. Blacker, C. Masullo, H. Schmidt, R.S. Doody, G. Spalletta, W.T. Longstreth, T.J. Fairchild, P. Bossù, O.L. Lopez, M.P. Frosch, E. Sacchinelli, B. Ghetti, Q. Yang, R.M. Huebinger, F. Jessen, S. Li, M.I. Kamboh, J. Morris, O. Sotolongo-Grau, M.J. Katz, C. Corcoran, M. Dunstan, A. Braddel, C. Thomas, A. Meggy, R. Marshall, A. Gerrish, J. Chapman, M. Aguilar, S. Taylor, M. Hill, M.D. Fairén, A. Hodges, B. Vellas, H. Soininen, I. Kloszewska, M. Daniilidou, J. Uphill, Y. Patel, J.T. Hughes, J. Lord, J. Turton, A.M. Hartmann, R. Cecchetti, C. Fenoglio, M. Serpente, M. Arcaro, C. Caltagirone, M.D. Orfei, A. Ciaramella, S. Pichler, M. Mayhaus, W. Gu, A. Lleó, J. Fortea, R. Blesa, I.S. Barber, K. Brookes, C. Cupidi, R.G. Maletta, D. Carrell, S. Sorbi, S. Moebus, M. Urbano, A. Pilotto, J. Kornhuber, P. Bosco, S. Todd, D. Craig, J. Johnston, M. Gill, B. Lawlor, A. Lynch, N.C. Fox, J. Hardy, R.L. Albin, L.G. Apostolova, S.E. Arnold, S. Asthana, C.S. Atwood, C.T. Baldwin, L.L. Barnes, S. Barral, T.G. Beach, J.T. Becker, E.H. Bigio, T.D. Bird, B.F. Boeve, J.D. Bowen, A. Boxer, J.R. Burke, J.M. Burns, J.D. Buxbaum, N.J. Cairns, C. Cao, C.S. Carlson, C.M. Carlsson, R.M. Carney, M.M. Carrasquillo, S.L. Carroll, C.C. Diaz, H.C. Chui, D.G. Clark, D.H. Cribbs, E.A. Crocco, C. Decarli, M. Dick, R. Duara, D.A. Evans, K.M. Faber, K.B. Fallon, D.W. 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Seshardi. - In: ALZHEIMER'S & DEMENTIA: DIAGNOSIS, ASSESSMENT & DISEASE MONITORING. - ISSN 2352-8729. - 10(2018 Jan 01), pp. 595-598. [10.1016/j.dadm.2018.08.008]

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

Fenoglio, C.;Serpente, M.;Arcaro, M.;Galimberti, D.;Scarpini, E.;
2018-01-01

Abstract

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.
Cholesteryl ester transfer protein; Genetics; HDL-C; Instrumental variables; Single nucleotide polymorphisms; Neurology (clinical); Psychiatry and Mental Health
Settore BIO/13 - Biologia Applicata
Settore MED/26 - Neurologia
ALZHEIMER'S & DEMENTIA: DIAGNOSIS, ASSESSMENT & DISEASE MONITORING
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/635452
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