Genetically elevated high‐density lipoprotein cholesterol through the cholesteryl ester transfer protein gene does not associate with risk of Alzheimer's disease. Issue 1 (21st September 2018)

• Record Type: Journal Article
• Authors: Peloso, Gina M.; van der Lee, Sven J.; Sims, R.; van der Lee, S.J.; Naj, A.C.; Bellenguez, C.; Badarinarayan, N.; Jakobsdottir, J.; Kunkle, B.W.; Boland, A.; Raybould, R.; Bis, J.C.; Martin, E.R.; Grenier‐Boley, B.; Heilmann‐Heimbach, S.; Chouraki, V.; Kuzma, A.B.; Sleegers, K.; Vronskaya, M.; Ruiz, A.; Graham, R.R.; Olaso, R.; Hoffmann, P.; Grove, M.L.; Vardarajan, B.N.; Hiltunen, M.; Nöthen, M.M.; White, C.C.; Hamilton‐Nelson, K.L.; Epelbaum, J.; Maier, W.; Choi, S.H.; Beecham, G.W.; Dulary, C.; Herms, S.; Smith, A.V.; Funk, C.C.; Derbois, ; Forstner, A.J.; Ahmad, S.; Li, H.; Bacq, D.; Harold, D.; Satizabal, C.L.; Valladares, O.; Squassina, A.; Thomas, R.; Brody, J.A.; Qu, L.; Sánchez‐Juan, P.; Morgan, T.; Wolters, F.J.; Zhao, Y.; Garcia, F.S.; Denning, N.; Fornage, M.; Malamon, J.; Naranjo, M.C.D.; Majounie, E.; Mosley, T.H.; Dombroski, B.; Wallon, D.; Lupton, M.K.; Dupuis, J.; Whitehead, P.; Fratiglioni, L.; Medway, C.; Jian, X.; Mukherjee, S.; Keller, L.; Brown, K.; Lin, H.; Cantwell, L.B.; Panza, F.; McGuinness, B.; Moreno‐Grau, S.; Burgess, J.D.; Solfrizzi, V.; Proitsi, P.; Adams, H.H.; Allen, M.; Seripa, D.; Pastor, P.; Cupples, L.A.; Price, N.D.; Hannequin, D.; Frank‐García, A.; Levy, D.; Chakrabarty, P.; Caffarra, P.; Giegling, I.; Beiser, A.S.; Giedraitis, V.; Hampel, H.; Garcia, M.E.; Wang, X.; Lannfelt, L.; Mecocci, P.; Eiriksdottir, G.; Crane, P.K.; Pasquier, F.; Boccardi, V.; Henández, I.; Barber, R.C.; Scherer, M.; Tarraga, L.; Adams, P.M.; Leber, M.; Chen, Y.; Albert, M.S.; Riedel‐Heller, S.; Emilsson, V.; Beekly, D.; Braae, A.; Schmidt, R.; Blacker, D.; Masullo, C.; Schmidt, H.; Doody, R.S.; Spalletta, G.; Longstreth, W.T.; Fairchild, T.J.; Bossù, P.; Lopez, O.L.; Frosch, M.P.; Sacchinelli, E.; Ghetti, B.; Yang, Q.; Huebinger, R.M.; Jessen, F.; Li, S.; Kamboh, M.I.; Morris, J.; Sotolongo‐Grau, O.; Katz, M.J.; Corcoran, C.; Dunstan, M.; Braddel, A.; Thomas, C.; Meggy, A.; Marshall, R.; Gerrish, A.; Chapman, J.; Aguilar, M.; Taylor, S.; Hill, M.; Fairén, M.D.; Hodges, A.; Vellas, B.; Soininen, H.; Kloszewska, I.; Daniilidou, M.; Uphill, J.; Patel, Y.; Hughes, J.T.; Lord, J.; Turton, J.; Hartmann, A.M.; Cecchetti, R.; Fenoglio, C.; Serpente, M.; Arcaro, M.; Caltagirone, C.; Orfei, M.D.; Ciaramella, A.; Pichler, S.; Mayhaus, M.; Gu, W.; Lleó, A.; Fortea, J.; Blesa, R.; Barber, I.S.; Brookes, K.; Cupidi, C.; Maletta, R.G.; 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, N.C.; Hardy, J.; Albin, R.L.; Apostolova, L.G.; Arnold, S.E.; Asthana, S.; Atwood, C.S.; Baldwin, C.T.; Barnes, L.L.; Barral, S.; Beach, T.G.; Becker, J.T.; Bigio, E.H.; Bird, T.D.; Boeve, B.F.; Bowen, J.D.; Boxer, A.; Burke, J.R.; Burns, J.M.; Buxbaum, J.D.; Cairns, N.J.; Cao, C.; Carlson, C.S.; Carlsson, C.M.; Carney, R.M.; Carrasquillo, M.M.; Carroll, S.L.; Diaz, C.C.; Chui, H.C.; Clark, D.G.; Cribbs, D.H.; Crocco, E.A.; DeCarli, C.; Dick, M.; Duara, R.; Evans, D.A.; Faber, K.M.; Fallon, K.B.; Fardo, D.W.; Farlow, M.R.; Ferris, S.; Foroud, T.M.; Galasko, D.R.; Gearing, M.; Geschwind, D.H.; Gilbert, J.R.; Graff‐Radford, N.R.; Green, R.C.; Growdon, J.H.; Hamilton, R.L.; Harrell, L.E.; Honig, L.S.; Huentelman, M.J.; Hulette, C.M.; Hyman, B.T.; Jarvik, G.P.; Abner, E.; Jin, L.W.; Jun, G.; Karydas, A.; Kaye, J.A.; Kim, R.; Kowall, N.W.; Kramer, J.H.; LaFerla, F.M.; Lah, J.J.; Leverenz, J.B.; Levey, A.I.; Li, G.; Lieberman, A.P.; Lunetta, K.L.; Lyketsos, C.G.; Marson, D.C.; Martiniuk, F.; Mash, D.C.; Masliah, E.; McCormick, W.C.; McCurry, S.M.; McDavid, A.N.; McKee, A.C.; Mesulam, M.; Miller, B.L.; Miller, C.A.; Miller, J.W.; Morris, J.C.; Murrell, J.R.; Myers, A.J.; O'Bryant, S.; Olichney, J.M.; Pankratz, V.S.; Parisi, J.E.; Paulson, H.L.; Perry, W.; Peskind, E.; Pierce, A.; Poon, W.W.; Potter, H.; Quinn, J.F.; Raj, A.; Raskind, M.; Reisberg, B.; Reitz, C.; Ringman, J.M.; Roberson, E.D.; Rogaeva, E.; Rosen, H.J.; Rosenberg, R.N.; Sager, M.A.; Saykin, A.J.; Schneider, J.A.; Schneider, L.S.; Seeley, W.W.; Smith, A.G.; Sonnen, J.A.; Spina, S.; Stern, R.A.; Swerdlow, R.H.; Tanzi, R.E.; Thornton‐Wells, T.A.; Trojanowski, J.Q.; Troncoso, J.C.; Van Deerlin, V.M.; Van Eldik, L.J.; Vinters, H.V.; Vonsattel, J.P.; Weintraub, S.; Welsh‐Bohmer, K.A.; Wilhelmsen, K.C.; Williamson, J.; Wingo, T.S.; Woltjer, R.L.; Wright, C.B.; Yu, C.E.; Yu, L.; Garzia, F.; Golamaully, F.; Septier, G.; Engelborghs, S.; Vandenberghe, R.; De Deyn, P.P.; Fernadez, C.M.; Benito, Y.A.; Thonberg, H.; Forsell, C.; Lilius, L.; Kinhult‐Stählbom, A.; Kilander, L.; Brundin, R.; Concari, L.; Helisalmi, S.; Koivisto, A.M.; Haapasalo, A.; Dermecourt, V.; Fievet, N.; Hanon, O.; Dufouil, C.; Brice, A.; Ritchie, K.; Dubois, B.; Himali, J.J.; Keene, C.D.; Tschanz, J.; Fitzpatrick, A.L.; Kukull, W.A.; Norton, M.; Aspelund, T.; Larson, E.B.; Munger, R.; Rotter, J.I.; Lipton, R.B.; Bullido, M.J.; Hofman, A.; Montine, T.J.; Coto, E.; Boerwinkle, E.; Petersen, R.C.; Alvarez, V.; Rivadeneira, F.; Reiman, E.M.; Gallo, M.; O'Donnell, C.J.; Reisch, J.S.; Bruni, A.C.; Royall, D.R.; Dichgans, M.; Sano, M.; Galimberti, D.; St George‐Hyslop, P.; Scarpini, E.; Tsuang, D.W.; Mancuso, M.; Bonuccelli, U.; Winslow, A.R.; Daniele, A.; Wu, C.K.; Peters, O.; Nacmias, B.; Riemenschneider, M.; Heun, R.; Brayne, C.; Rubinsztein, D.C.; Bras, J.; Guerreiro, R.; Al‐Chalabi, A.; Shaw, C.E.; Collinge, J.; Mann, D.; Tsolaki, M.; Clarimón, J.; Sussams, R.; Lovestone, S.; O'Donovan, M.C.; Owen, M.J.; Behrens, T.W.; Mead, S.; Goate, A.M.; Uitterlinden, A.G.; Holmes, C.; Cruchaga, C.; Ingelsson, M.; Bennett, D.A.; Powell, J.; Golde, T.E.; Graff, C.; De Jager, P.L.; Morgan, K.; Ertekin‐Taner, N.; Combarros, O.; Psaty, B.M.; Passmore, P.; Younkin, S.G.; Berr, C.; Gudnason, V.; Rujescu, D.; Dickson, D.W.; Dartigues, J.F.; DeStefano, A.L.; Ortega‐Cubero, S.; Hakonarson, H.; Campion, D.; Boada, M.; Kauwe, J.K.; Farrer, L.A.; Van Broeckhoven, C.; Ikram, M.A.; Jones, L.; Haines, J.L.; Tzourio, C.; Launer, L.J.; Escott‐Price, V.; Mayeux, R.; Deleuze, J.F.; Amin, N.; Holmans, P.A.; Pericak‐Vance, M.A.; Amouyel, P.; van Duijn, C.M.; Ramirez, A.; Wang, L.S.; Lambert, J.C.; Seshadri, S.; Williams, J.; Schellenberg, G.D.; Destefano, Anita L.; Seshardi, Sudha;
• Is Part Of: Alzheimer's & dementia. Volume 10:Issue 1(2018)
• Page Start: 595
• Page End: 598
• Publication Date: 2018-09-21
• Subjects: Genetics -- HDL‐C -- Single nucleotide polymorphisms -- Instrumental variables -- Cholesteryl ester transfer protein; Alzheimer's disease -- Periodicals; Alzheimer's disease -- Diagnosis -- Periodicals; Dementia -- Periodicals; Dementia -- Diagnosis -- Periodicals; 616.831
• DOI: 10.1016/j.dadm.2018.08.008
• Languages: English
• ISSNs: 2352-8729

Abstract

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. Highlights: CETP SNPs were not associated with AD in a large sample of AD cases/controls. Genetically predicted HDL‐C through CETP does not associate with AD.