Genetically elevated high‐density lipoprotein cholesterol through the cholesteryl ester transfer protein gene does not associate with risk of Alzheimer's disease
Year: 2018
Type: article
Study design: Observational Study
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.
Authors: Gina M. Peloso, Sven J. van der Lee, International Genomics of Alzheimer's Project (IGAP), 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, 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. Fardo, M.R. Farlow, S. Ferris, T.M. Foroud, D.R. Galasko, M. Gearing, D.H. Geschwind, J.R. Gilbert, N.R. Graff‐Radford, R.C. Green, J.H. Growdon, R.L. Hamilton, L.E. Harrell, L.S. Honig, M.J. Huentelman, C.M. Hulette, B.T. Hyman, G.P. Jarvik, E. Abner, L.W. Jin, G. Jun, A. Karydas, J.A. Kaye, R. Kim, N.W. Kowall, J.H. Kramer, F.M. LaFerla, J.J. Lah, J.B. Leverenz, A.I. Levey, G. Li, A.P. Lieberman, K.L. Lunetta, C.G. Lyketsos, D.C. Marson, F. Martiniuk, D.C. Mash, E. Masliah, W.C. McCormick, S.M. McCurry, A.N. McDavid, A.C. McKee, M. Mesulam, B.L. Miller, C.A. Miller, J.W. Miller, J.C. Morris, J.R. Murrell, A.J. Myers, S. O'Bryant, J.M. Olichney, V.S. Pankratz, J.E. Parisi, H.L. Paulson, W. Perry, E. Peskind, A. Pierce, W.W. Poon, H. Potter, J.F. Quinn, A. Raj, M. Raskind, B. Reisberg, C. Reitz, J.M. Ringman, E.D. Roberson, E. Rogaeva, H.J. Rosen, R.N. Rosenberg, M.A. Sager, A.J. Saykin, J.A. Schneider, L.S. Schneider, W.W. Seeley, A.G. Smith, J.A. Sonnen, S. Spina, R.A. Stern, R.H. Swerdlow, R.E. Tanzi, T.A. Thornton‐Wells, J.Q. Trojanowski, J.C. Troncoso, V.M. Van Deerlin, L.J. Van Eldik, H.V. Vinters, J.P. Vonsattel, S. Weintraub, K.A. Welsh‐Bohmer, K.C. Wilhelmsen, J. Williamson, T.S. Wingo, R.L. Woltjer, C.B. Wright, C.E. Yu, L. Yu, F. Garzia, F. Golamaully, G. Septier, S. Engelborghs, R. Vandenberghe, P.P. De Deyn, C.M. Fernadez, Y.A. Benito, H. Thonberg, C. Forsell, L. Lilius, A. Kinhult‐Stählbom, L. Kilander, R. Brundin, L. Concari, S. Helisalmi, A.M. Koivisto, A. Haapasalo, V. Dermecourt, N. Fievet, O. Hanon, C. Dufouil, A. Brice, K. Ritchie, B. Dubois, J.J. Himali, C.D. Keene, J. Tschanz, A.L. Fitzpatrick, W.A. Kukull, M. Norton, T. Aspelund, E.B. Larson, R. Munger, J.I. Rotter, R.B. Lipton, M.J. Bullido, A. Hofman, T.J. Montine, E. Coto, E. Boerwinkle, R.C. Petersen, V. Alvarez, F. Rivadeneira, E.M. Reiman, M. Gallo, C.J. O'Donnell, J.S. Reisch, A.C. Bruni, D.R. Royall, M. Dichgans, M. Sano, D. Galimberti, P. St George‐Hyslop, E. Scarpini, D.W. Tsuang, M. Mancuso, U. Bonuccelli, A.R. Winslow, A. Daniele, C.K. Wu, GERAD/PERADES, CHARGE, ADGC, EADI, O. Peters, B. Nacmias, M. Riemenschneider, R. Heun, C. Brayne, D.C. Rubinsztein, J. Bras, R. Guerreiro, A. Al‐Chalabi, C.E. Shaw, J. Collinge, D. Mann, M. Tsolaki, J. Clarimón, R. Sussams, S. Lovestone, M.C. O'Donovan, M.J. Owen, T.W. Behrens, S. Mead, A.M. Goate, A.G. Uitterlinden, C. Holmes, C. Cruchaga, M. Ingelsson, D.A. Bennett, J. Powell, T.E. Golde, C. Graff, P.L. De Jager, K. Morgan, N. Ertekin‐Taner, O. Combarros, B.M. Psaty, P. Passmore, S.G. Younkin, C. Berr, V. Gudnason, D. Rujescu, D.W. Dickson, J.F. Dartigues, A.L. DeStefano, S. Ortega‐Cubero, H. Hakonarson, D. Campion, M. Boada, J.K. Kauwe, L.A. Farrer, C. Van Broeckhoven, M.A. Ikram, L. Jones, J.L. Haines, C. Tzourio, L.J. Launer, V. Escott‐Price, R. Mayeux, J.F. Deleuze, N. Amin, P.A. Holmans, M.A. Pericak‐Vance, P. Amouyel, C.M. van Duijn, A. Ramirez, L.S. Wang, J.C. Lambert, S. Seshadri, J. Williams, G.D. Schellenberg, Anita L. Destefano, Sudha Seshardi
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,540
Awards: G1017859460, G1194337659, G1212982470, Michigan Alzheimer's Disease Core Center, UC Davis Alzheimer's Disease Core Center, G1353455142, G1379949353, G1602390028, G1875193427, G1888650583, Integrative translational discovery of vascular risk factors in aging and dementia, G232440474, G2630878680, G2908616768, G36433118, G40706755, G4427631003, G4557674082, APOEomic: Searching for APOE interacting risk factors using omics data, Risk Factors, Pathology, and Clinical Expressions of AD, G5056103449, G5218064391, Discovering lipoprotein lipase pathway variants that protect against CHD, G5370164845, G5558075022, G5600171757, NIHR Senior Investigator Award, Alzheimer's Disease Research Center, G7264467602, G7431531211, G828200374, G9000041750, G9000047714, G9000106852, G9000144860, G9000185046, G9000270168, Frontotemporal Dementia: Genes, Images, and Emotions, Antecedent Biomarkers for Alzheimer Disease: The Adult Children Study, G983864884
OpenAlex ID: W2892466876