Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease.

Publication Type:

Journal Article

Authors:

Naj, Adam C; Jun, Gyungah; Beecham, Gary W; Wang, Li-San; Vardarajan, Badri Narayan; Buros, Jacqueline; Gallins, Paul J; Buxbaum, Joseph D; Jarvik, Gail P; Crane, Paul K; Larson, Eric B; Bird, Thomas D; Boeve, Bradley F; Graff-Radford, Neill R; De Jager, Philip L; Evans, Denis; Schneider, Julie A; Carrasquillo, Minerva M; Ertekin-Taner, Nilufer; Younkin, Steven G; Cruchaga, Carlos; Kauwe, John S K; Nowotny, Petra; Kramer, Patricia; Hardy, John; Huentelman, Matthew J; Myers, Amanda J; Barmada, Michael M; Demirci, F Yesim; Baldwin, Clinton T; Green, Robert C; Rogaeva, Ekaterina; St George-Hyslop, Peter; Arnold, Steven E; Barber, Robert; Beach, Thomas; Bigio, Eileen H; Bowen, James D; Boxer, Adam; Burke, James R; Cairns, Nigel J; Carlson, Christopher S; Carney, Regina M; Carroll, Steven L; Chui, Helena C; Clark, David G; Corneveaux, Jason; Cotman, Carl W; Cummings, Jeffrey L; DeCarli, Charles; DeKosky, Steven T; Diaz-Arrastia, Ramon; Dick, Malcolm; Dickson, Dennis W; Ellis, William G; Faber, Kelley M; Fallon, Kenneth B; Farlow, Martin R; Ferris, Steven; Frosch, Matthew P; Galasko, Douglas R; Ganguli, Mary; Gearing, Marla; Geschwind, Daniel H; Ghetti, Bernardino; Gilbert, John R; Gilman, Sid; Giordani, Bruno; Glass, Jonathan D; Growdon, John H; Hamilton, Ronald L; Harrell, Lindy E; Head, Elizabeth; Honig, Lawrence S; Hulette, Christine M; Hyman, Bradley T; Jicha, Gregory A; Jin, Lee-Way; Johnson, Nancy; Karlawish, Jason; Karydas, Anna; Kaye, Jeffrey A; Kim, Ronald; Koo, Edward H; Kowall, Neil W; Lah, James J; Levey, Allan I; Lieberman, Andrew P; Lopez, Oscar L; Mack, Wendy J; Marson, Daniel C; Martiniuk, Frank; Mash, Deborah C; Masliah, Eliezer; McCormick, Wayne C; McCurry, Susan M; McDavid, Andrew N; McKee, Ann C; Mesulam, Marsel; Miller, Bruce L; Miller, Carol A; Miller, Joshua W; Parisi, Joseph E; Perl, Daniel P; Peskind, Elaine; Petersen, Ronald C; Poon, Wayne W; Quinn, Joseph F; Rajbhandary, Ruchita A; Raskind, Murray; Reisberg, Barry; Ringman, John M; Roberson, Erik D; Rosenberg, Roger N; Sano, Mary; Schneider, Lon S; Seeley, William; Shelanski, Michael L; Slifer, Michael A; Smith, Charles D; Sonnen, Joshua A; Spina, Salvatore; Stern, Robert A; Tanzi, Rudolph E; Trojanowski, John Q; Troncoso, Juan C; Van Deerlin, Vivianna M; Vinters, Harry V; Vonsattel, Jean Paul; Weintraub, Sandra; Welsh-Bohmer, Kathleen A; Williamson, Jennifer; Woltjer, Randall L; Cantwell, Laura B; Dombroski, Beth A; Beekly, Duane; Lunetta, Kathryn L; Martin, Eden R; Kamboh, M Ilyas; Saykin, Andrew J; Reiman, Eric M; Bennett, David A; Morris, John C; Montine, Thomas J; Goate, Alison M; Blacker, Deborah; Tsuang, Debby W; Hakonarson, Hakon; Kukull, Walter A; Foroud, Tatiana M; Haines, Jonathan L; Mayeux, Richard; Pericak-Vance, Margaret A; Farrer, Lindsay A; Schellenberg, Gerard D

Source:

Nature genetics, Volume 43, Issue 5, p.436-41 (2011)

Keywords:

2011, Adaptor Proteins, Signal Transducing, Age of Onset, Aged, Aged, 80 and over, Alzheimer Disease, Antigens, CD, Antigens, Differentiation, Myelomonocytic, Cohort Studies, Cytoskeletal Proteins, Databases, Genetic, Female, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Humans, Male, Membrane Proteins, Multigene Family, Polymorphism, Single Nucleotide, Public Health Sciences Division, Receptor, EphA1

Abstract:

The Alzheimer Disease Genetics Consortium (ADGC) performed a genome-wide association study of late-onset Alzheimer disease using a three-stage design consisting of a discovery stage (stage 1) and two replication stages (stages 2 and 3). Both joint analysis and meta-analysis approaches were used. We obtained genome-wide significant results at MS4A4A (rs4938933; stages 1 and 2, meta-analysis P (P(M)) = 1.7 × 10(-9), joint analysis P (P(J)) = 1.7 × 10(-9); stages 1, 2 and 3, P(M) = 8.2 × 10(-12)), CD2AP (rs9349407; stages 1, 2 and 3, P(M) = 8.6 × 10(-9)), EPHA1 (rs11767557; stages 1, 2 and 3, P(M) = 6.0 × 10(-10)) and CD33 (rs3865444; stages 1, 2 and 3, P(M) = 1.6 × 10(-9)). We also replicated previous associations at CR1 (rs6701713; P(M) = 4.6 × 10(-10), P(J) = 5.2 × 10(-11)), CLU (rs1532278; P(M) = 8.3 × 10(-8), P(J) = 1.9 × 10(-8)), BIN1 (rs7561528; P(M) = 4.0 × 10(-14), P(J) = 5.2 × 10(-14)) and PICALM (rs561655; P(M) = 7.0 × 10(-11), P(J) = 1.0 × 10(-10)), but not at EXOC3L2, to late-onset Alzheimer's disease susceptibility.