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Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease.

ABSTRACT: Eleven susceptibility loci for late-onset Alzheimer's disease (LOAD) were identified by previous studies; however, a large portion of the genetic risk for this disease remains unexplained. We conducted a large, two-stage meta-analysis of genome-wide association studies (GWAS) in individuals of European ancestry. In stage 1, we used genotyped and imputed data (7,055,881 SNPs) to perform meta-analysis on 4 previously published GWAS data sets consisting of 17,008 Alzheimer's disease cases and 37,154 controls. In stage 2, 11,632 SNPs were genotyped and tested for association in an independent set of 8,572 Alzheimer's disease cases and 11,312 controls. In addition to the APOE locus (encoding apolipoprotein E), 19 loci reached genome-wide significance (P < 5 × 10(-8)) in the combined stage 1 and stage 2 analysis, of which 11 are newly associated with Alzheimer's disease.

SUBMITTER: Lambert JC 

PROVIDER: S-EPMC3896259 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease.

Lambert J C JC   Ibrahim-Verbaas C A CA   Harold D D   Naj A C AC   Sims R R   Bellenguez C C   DeStafano A L AL   Bis J C JC   Beecham G W GW   Grenier-Boley B B   Russo G G   Thorton-Wells T A TA   Jones N N   Smith A V AV   Chouraki V V   Thomas C C   Ikram M A MA   Zelenika D D   Vardarajan B N BN   Kamatani Y Y   Lin C F CF   Gerrish A A   Gerrish A A   Schmidt H H   Kunkle B B   Dunstan M L ML   Ruiz A A   Bihoreau M T MT   Choi S H SH   Reitz C C   Pasquier F F   Cruchaga C C   Craig D D   Amin N N   Berr C C   Lopez O L OL   De Jager P L PL   Deramecourt V V   Johnston J A JA   Evans D D   Lovestone S S   Letenneur L L   Morón F J FJ   Rubinsztein D C DC   Eiriksdottir G G   Sleegers K K   Goate A M AM   Fiévet N N   Huentelman M W MW   Gill M M   Brown K K   Kamboh M I MI   Keller L L   Barberger-Gateau P P   McGuiness B B   Larson E B EB   Green R R   Myers A J AJ   Dufouil C C   Todd S S   Wallon D D   Love S S   Rogaeva E E   Gallacher J J   St George-Hyslop P P   Clarimon J J   Lleo A A   Bayer A A   Tsuang D W DW   Yu L L   Tsolaki M M   Bossù P P   Spalletta G G   Proitsi P P   Collinge J J   Sorbi S S   Sanchez-Garcia F F   Fox N C NC   Hardy J J   Deniz Naranjo M C MC   Bosco P P   Clarke R R   Brayne C C   Galimberti D D   Mancuso M M   Matthews F F   Moebus S S   Mecocci P P   Del Zompo M M   Maier W W   Hampel H H   Pilotto A A   Bullido M M   Panza F F   Caffarra P P   Nacmias B B   Gilbert J R JR   Mayhaus M M   Lannefelt L L   Hakonarson H H   Pichler S S   Carrasquillo M M MM   Ingelsson M M   Beekly D D   Alvarez V V   Zou F F   Valladares O O   Younkin S G SG   Coto E E   Hamilton-Nelson K L KL   Gu W W   Razquin C C   Pastor P P   Mateo I I   Owen M J MJ   Faber K M KM   Jonsson P V PV   Combarros O O   O'Donovan M C MC   Cantwell L B LB   Soininen H H   Blacker D D   Mead S S   Mosley T H TH   Bennett D A DA   Harris T B TB   Fratiglioni L L   Holmes C C   de Bruijn R F RF   Passmore P P   Montine T J TJ   Bettens K K   Rotter J I JI   Brice A A   Morgan K K   Foroud T M TM   Kukull W A WA   Hannequin D D   Powell J F JF   Nalls M A MA   Ritchie K K   Lunetta K L KL   Kauwe J S JS   Boerwinkle E E   Riemenschneider M M   Boada M M   Hiltuenen M M   Martin E R ER   Schmidt R R   Rujescu D D   Wang L S LS   Dartigues J F JF   Mayeux R R   Tzourio C C   Hofman A A   Nöthen M M MM   Graff C C   Psaty B M BM   Jones L L   Haines J L JL   Holmans P A PA   Lathrop M M   Pericak-Vance M A MA   Launer L J LJ   Farrer L A LA   van Duijn C M CM   Van Broeckhoven C C   Moskvina V V   Seshadri S S   Williams J J   Schellenberg G D GD   Amouyel P P  

Nature genetics 20131027 12

Eleven susceptibility loci for late-onset Alzheimer's disease (LOAD) were identified by previous studies; however, a large portion of the genetic risk for this disease remains unexplained. We conducted a large, two-stage meta-analysis of genome-wide association studies (GWAS) in individuals of European ancestry. In stage 1, we used genotyped and imputed data (7,055,881 SNPs) to perform meta-analysis on 4 previously published GWAS data sets consisting of 17,008 Alzheimer's disease cases and 37,15  ...[more]

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