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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 436-443 |
| Number of pages | 8 |
| Journal | Nature Genetics |
| Volume | 43 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 2011 |
ASJC Scopus subject areas
- Genetics
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Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease. / 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; George-Hyslop, Peter St; 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.
In: Nature Genetics, Vol. 43, No. 5, 05.2011, p. 436-443.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease
AU - Naj, Adam C.
AU - Jun, Gyungah
AU - Beecham, Gary W.
AU - Wang, Li San
AU - Vardarajan, Badri Narayan
AU - Buros, Jacqueline
AU - Gallins, Paul J.
AU - Buxbaum, Joseph D.
AU - Jarvik, Gail P.
AU - Crane, Paul K.
AU - Larson, Eric B.
AU - Bird, Thomas D.
AU - Boeve, Bradley F.
AU - Graff-Radford, Neill R.
AU - De Jager, Philip L.
AU - Evans, Denis
AU - Schneider, Julie A.
AU - Carrasquillo, Minerva M.
AU - Ertekin-Taner, Nilufer
AU - Younkin, Steven G.
AU - Cruchaga, Carlos
AU - Kauwe, John S K
AU - Nowotny, Petra
AU - Kramer, Patricia
AU - Hardy, John
AU - Huentelman, Matthew J.
AU - Myers, Amanda J.
AU - Barmada, Michael M.
AU - Demirci, F. Yesim
AU - Baldwin, Clinton T.
AU - Green, Robert C.
AU - Rogaeva, Ekaterina
AU - George-Hyslop, Peter St
AU - Arnold, Steven E.
AU - Barber, Robert
AU - Beach, Thomas
AU - Bigio, Eileen H.
AU - Bowen, James D.
AU - Boxer, Adam
AU - Burke, James R.
AU - Cairns, Nigel J.
AU - Carlson, Chris S.
AU - Carney, Regina M.
AU - Carroll, Steven L.
AU - Chui, Helena C.
AU - Clark, David G.
AU - Corneveaux, Jason
AU - Cotman, Carl W.
AU - Cummings, Jeffrey L.
AU - DeCarli, Charles
AU - Dekosky, Steven T.
AU - Diaz-Arrastia, Ramon
AU - Dick, Malcolm
AU - Dickson, Dennis W.
AU - Ellis, William G.
AU - Faber, Kelley M.
AU - Fallon, Kenneth B.
AU - Farlow, Martin R.
AU - Ferris, Steven
AU - Frosch, Matthew P.
AU - Galasko, Douglas R.
AU - Ganguli, Mary
AU - Gearing, Marla
AU - Geschwind, Daniel H.
AU - Ghetti, Bernardino
AU - Gilbert, John R.
AU - Gilman, Sid
AU - Giordani, Bruno
AU - Glass, Jonathan D.
AU - Growdon, John H.
AU - Hamilton, Ronald L.
AU - Harrell, Lindy E.
AU - Head, Elizabeth
AU - Honig, Lawrence S.
AU - Hulette, Christine M.
AU - Hyman, Bradley T.
AU - Jicha, Gregory A.
AU - Jin, Lee-Way
AU - Johnson, Nancy
AU - Karlawish, Jason
AU - Karydas, Anna
AU - Kaye, Jeffrey A.
AU - Kim, Ronald
AU - Koo, Edward H.
AU - Kowall, Neil W.
AU - Lah, James J.
AU - Levey, Allan I.
AU - Lieberman, Andrew P.
AU - Lopez, Oscar L.
AU - MacK, Wendy J.
AU - Marson, Daniel C.
AU - Martiniuk, Frank
AU - Mash, Deborah C.
AU - Masliah, Eliezer
AU - McCormick, Wayne C.
AU - McCurry, Susan M.
AU - McDavid, Andrew N.
AU - McKee, Ann C.
AU - Mesulam, Marsel
AU - Miller, Bruce L.
AU - Miller, Carol A.
AU - Miller, Joshua W.
AU - Parisi, Joseph E.
AU - Perl, Daniel P.
AU - Peskind, Elaine
AU - Petersen, Ronald C.
AU - Poon, Wayne W.
AU - Quinn, Joseph F.
AU - Rajbhandary, Ruchita A.
AU - Raskind, Murray
AU - Reisberg, Barry
AU - Ringman, John M.
AU - Roberson, Erik D.
AU - Rosenberg, Roger N.
AU - Sano, Mary
AU - Schneider, Lon S.
AU - Seeley, William
AU - Shelanski, Michael L.
AU - Slifer, Michael A.
AU - Smith, Charles D.
AU - Sonnen, Joshua A.
AU - Spina, Salvatore
AU - Stern, Robert A.
AU - Tanzi, Rudolph E.
AU - Trojanowski, John Q.
AU - Troncoso, Juan C.
AU - Van Deerlin, Vivianna M.
AU - Vinters, Harry V.
AU - Vonsattel, Jean Paul
AU - Weintraub, Sandra
AU - Welsh-Bohmer, Kathleen A.
AU - Williamson, Jennifer
AU - Woltjer, Randall L.
AU - Cantwell, Laura B.
AU - Dombroski, Beth A.
AU - Beekly, Duane
AU - Lunetta, Kathryn L.
AU - Martin, Eden R.
AU - Kamboh, M. Ilyas
AU - Saykin, Andrew J.
AU - Reiman, Eric M.
AU - Bennett, David A.
AU - Morris, John C.
AU - Montine, Thomas J.
AU - Goate, Alison M.
AU - Blacker, Deborah
AU - Tsuang, Debby W.
AU - Hakonarson, Hakon
AU - Kukull, Walter A.
AU - Foroud, Tatiana M.
AU - Haines, Jonathan L.
AU - Mayeux, Richard
AU - Pericak-Vance, Margaret A.
AU - Farrer, Lindsay A.
AU - Schellenberg, Gerard D.
PY - 2011/5
Y1 - 2011/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=79955464911&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79955464911&partnerID=8YFLogxK
U2 - 10.1038/ng.801
DO - 10.1038/ng.801
M3 - Article
C2 - 21460841
AN - SCOPUS:79955464911
VL - 43
SP - 436
EP - 443
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 5
ER -