Common variants in MS4A4/MS4A6E, CD2uAP, CD33, and EPHA1 are associated with late-onset Alzheimer’s disease

The Alzheimer Disease Genetics Consortium (ADGC) performed a genome-wide association study (GWAS) of late-onset Alzheimer disease (LOAD) using a 3 stage design consisting of a discovery stage (Stage 1) and two replication stages (Stages 2 and 3). Both joint and meta-analysis analysis approaches were...

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Autores principales: 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, Deerlin, Vivianna M Van, 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
Formato: Texto
Lenguaje:English
Publicado: 2011
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3090745/
https://www.ncbi.nlm.nih.gov/pubmed/21460841
http://dx.doi.org/10.1038/ng.801
Descripción
Sumario:The Alzheimer Disease Genetics Consortium (ADGC) performed a genome-wide association study (GWAS) of late-onset Alzheimer disease (LOAD) using a 3 stage design consisting of a discovery stage (Stage 1) and two replication stages (Stages 2 and 3). Both joint and meta-analysis analysis approaches were used. We obtained genome-wide significant results at MS4A4A [rs4938933; Stages 1+2, meta-analysis (P(M)) = 1.7 × 10(−9), joint analysis (P(J)) = 1.7 × 10(−9;) Stages 1–3, P(M) = 8.2 × 10(−12)], CD2AP (rs9349407; Stages 1–3, P(M) = 8.6 × 10(−9)), EPHA1 (rs11767557; Stages 1–3 P(M) = 6.0 × 10(−10)), and CD33 (rs3865444; Stages 1–3, P(M) = 1.6 × 10(−9)). We confirmed that 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 EXOC3L2 are LOAD risk loci(1–3).

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