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Meta-Analysis
. 2013 Dec;45(12):1452-8.
doi: 10.1038/ng.2802. Epub 2013 Oct 27.

Meta-analysis of 74,046 Individuals Identifies 11 New Susceptibility Loci for Alzheimer's Disease

J C LambertC A Ibrahim-VerbaasD HaroldA C NajR SimsC BellenguezA L DeStafanoJ C BisG W BeechamB Grenier-BoleyG RussoT A Thorton-WellsN JonesA V SmithV ChourakiC ThomasM A IkramD ZelenikaB N VardarajanY KamataniC F LinA GerrishH SchmidtB KunkleM L DunstanA RuizM T BihoreauS H ChoiC ReitzF PasquierC CruchagaD CraigN AminC BerrO L LopezP L De JagerV DeramecourtJ A JohnstonD EvansS LovestoneL LetenneurF J MorónD C RubinszteinG EiriksdottirK SleegersA M GoateN FiévetM W HuentelmanM GillK BrownM I KambohL KellerP Barberger-GateauB McGuinessE B LarsonR GreenA J MyersC DufouilS ToddD WallonS LoveE RogaevaJ GallacherP St George-HyslopJ ClarimonA LleoA BayerD W TsuangL YuM TsolakiP BossùG SpallettaP ProitsiJ CollingeS SorbiF Sanchez-GarciaN C FoxJ HardyM C Deniz NaranjoP BoscoR ClarkeC BrayneD GalimbertiM MancusoF MatthewsEuropean Alzheimer's Disease Initiative (EADI)Genetic and Environmental Risk in Alzheimer's DiseaseAlzheimer's Disease Genetic ConsortiumCohorts for Heart and Aging Research in Genomic EpidemiologyS MoebusP MecocciM Del ZompoW MaierH HampelA PilottoM BullidoF PanzaP CaffarraB NacmiasJ R GilbertM MayhausL LannefeltH HakonarsonS PichlerM M CarrasquilloM IngelssonD BeeklyV AlvarezF ZouO ValladaresS G YounkinE CotoK L Hamilton-NelsonW GuC RazquinP PastorI MateoM J OwenK M FaberP V JonssonO CombarrosM C O'DonovanL B CantwellH SoininenD BlackerS MeadT H Mosley JrD A BennettT B HarrisL FratiglioniC HolmesR F de BruijnP PassmoreT J MontineK BettensJ I RotterA BriceK MorganT M ForoudW A KukullD HannequinJ F PowellM A NallsK RitchieK L LunettaJ S KauweE BoerwinkleM RiemenschneiderM BoadaM HiltuenenE R MartinR SchmidtD RujescuL S WangJ F DartiguesR MayeuxC TzourioA HofmanM M NöthenC GraffB M PsatyL JonesJ L HainesP A HolmansM LathropM A Pericak-VanceL J LaunerL A FarrerC M van DuijnC Van BroeckhovenV MoskvinaS SeshadriJ WilliamsG D SchellenbergP Amouyel
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Free PMC article
Meta-Analysis

Meta-analysis of 74,046 Individuals Identifies 11 New Susceptibility Loci for Alzheimer's Disease

J C Lambert et al. Nat Genet. .
Free PMC article

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.

Figures

Figure 1
Figure 1
Manhattan plot of stage 1 for genome-wide association with Alzheimer’s disease (17,008 cases and 37,154 controls). The threshold for genome-wide significance (P < 5 × 10−8) is indicated by the red line. Genes previously identified by GWAS are shown in black, and newly associated genes are shown in red. Red diamonds represent SNPs with the smallest P values in the overall analysis.
Figure 2
Figure 2
Regional plot for the PTK2B-CLU locus (17,008 cases and 37,154 controls).

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