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


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.

SUBMITTER: Naj AC 

PROVIDER: S-EPMC3090745 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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

Naj Adam C AC   Jun Gyungah G   Beecham Gary W GW   Wang Li-San LS   Vardarajan Badri Narayan BN   Buros Jacqueline J   Gallins Paul J PJ   Buxbaum Joseph D JD   Jarvik Gail P GP   Crane Paul K PK   Larson Eric B EB   Bird Thomas D TD   Boeve Bradley F BF   Graff-Radford Neill R NR   De Jager Philip L PL   Evans Denis D   Schneider Julie A JA   Carrasquillo Minerva M MM   Ertekin-Taner Nilufer N   Younkin Steven G SG   Cruchaga Carlos C   Kauwe John S K JS   Nowotny Petra P   Kramer Patricia P   Hardy John J   Huentelman Matthew J MJ   Myers Amanda J AJ   Barmada Michael M MM   Demirci F Yesim FY   Baldwin Clinton T CT   Green Robert C RC   Rogaeva Ekaterina E   St George-Hyslop Peter P   Arnold Steven E SE   Barber Robert R   Beach Thomas T   Bigio Eileen H EH   Bowen James D JD   Boxer Adam A   Burke James R JR   Cairns Nigel J NJ   Carlson Chris S CS   Carney Regina M RM   Carroll Steven L SL   Chui Helena C HC   Clark David G DG   Corneveaux Jason J   Cotman Carl W CW   Cummings Jeffrey L JL   DeCarli Charles C   DeKosky Steven T ST   Diaz-Arrastia Ramon R   Dick Malcolm M   Dickson Dennis W DW   Ellis William G WG   Faber Kelley M KM   Fallon Kenneth B KB   Farlow Martin R MR   Ferris Steven S   Frosch Matthew P MP   Galasko Douglas R DR   Ganguli Mary M   Gearing Marla M   Geschwind Daniel H DH   Ghetti Bernardino B   Gilbert John R JR   Gilman Sid S   Giordani Bruno B   Glass Jonathan D JD   Growdon John H JH   Hamilton Ronald L RL   Harrell Lindy E LE   Head Elizabeth E   Honig Lawrence S LS   Hulette Christine M CM   Hyman Bradley T BT   Jicha Gregory A GA   Jin Lee-Way LW   Johnson Nancy N   Karlawish Jason J   Karydas Anna A   Kaye Jeffrey A JA   Kim Ronald R   Koo Edward H EH   Kowall Neil W NW   Lah James J JJ   Levey Allan I AI   Lieberman Andrew P AP   Lopez Oscar L OL   Mack Wendy J WJ   Marson Daniel C DC   Martiniuk Frank F   Mash Deborah C DC   Masliah Eliezer E   McCormick Wayne C WC   McCurry Susan M SM   McDavid Andrew N AN   McKee Ann C AC   Mesulam Marsel M   Miller Bruce L BL   Miller Carol A CA   Miller Joshua W JW   Parisi Joseph E JE   Perl Daniel P DP   Peskind Elaine E   Petersen Ronald C RC   Poon Wayne W WW   Quinn Joseph F JF   Rajbhandary Ruchita A RA   Raskind Murray M   Reisberg Barry B   Ringman John M JM   Roberson Erik D ED   Rosenberg Roger N RN   Sano Mary M   Schneider Lon S LS   Seeley William W   Shelanski Michael L ML   Slifer Michael A MA   Smith Charles D CD   Sonnen Joshua A JA   Spina Salvatore S   Stern Robert A RA   Tanzi Rudolph E RE   Trojanowski John Q JQ   Troncoso Juan C JC   Van Deerlin Vivianna M VM   Vinters Harry V HV   Vonsattel Jean Paul JP   Weintraub Sandra S   Welsh-Bohmer Kathleen A KA   Williamson Jennifer J   Woltjer Randall L RL   Cantwell Laura B LB   Dombroski Beth A BA   Beekly Duane D   Lunetta Kathryn L KL   Martin Eden R ER   Kamboh M Ilyas MI   Saykin Andrew J AJ   Reiman Eric M EM   Bennett David A DA   Morris John C JC   Montine Thomas J TJ   Goate Alison M AM   Blacker Deborah D   Tsuang Debby W DW   Hakonarson Hakon H   Kukull Walter A WA   Foroud Tatiana M TM   Haines Jonathan L JL   Mayeux Richard R   Pericak-Vance Margaret A MA   Farrer Lindsay A LA   Schellenberg Gerard D GD  

Nature genetics 20110403 5


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)),  ...[more]

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