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

  • Author(s): 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 SK;
  • 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, Chris 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
  • et al.

Published Web Location

https://doi.org/10.1038/ng.801Creative Commons 'BY' version 4.0 license
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.

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