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

TitleMeta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease.
Publication TypeJournal Article
Year of Publication2013
AuthorsLambert JC, Ibrahim-Verbaas CA, Harold D, Naj AC, Sims R, Bellenguez C, DeStafano AL, Bis JC, Beecham GW, Grenier-Boley B et al.
Corporate AuthorsEuropean Alzheimer's Disease Initiative(EADI), Genetic and Environmental Risk in Alzheimer's Disease, Alzheimer's Disease Genetic Consortium, Cohorts for Heart and Aging Research in Genomic Epidemiology
JournalNat Genet
Volume45
Issue12
Pagination1452-8
Date Published2013 Dec
ISSN1546-1718
KeywordsAge of Onset, Aged, Aged, 80 and over, Alzheimer Disease, Case-Control Studies, Cohort Studies, Female, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide
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.

DOI10.1038/ng.2802
Alternate JournalNat. Genet.
PubMed ID24162737
PubMed Central IDPMC3896259
Grant ListMR/K013041/1 / / Medical Research Council / United Kingdom
G0801306 / / Medical Research Council / United Kingdom
U01 HG006375 / HG / NHGRI NIH HHS / United States
MC_U123160657 / / Medical Research Council / United Kingdom
R01 AG016495 / AG / NIA NIH HHS / United States
P50 AG005131 / AG / NIA NIH HHS / United States
U24 AG021886 / AG / NIA NIH HHS / United States
K25 AG041906 / AG / NIA NIH HHS / United States
MC_U123160651 / / Medical Research Council / United Kingdom
U01 AG032984 / AG / NIA NIH HHS / United States
MC_U105292687 / / Medical Research Council / United Kingdom
P50 AG008702 / AG / NIA NIH HHS / United States
/ / Medical Research Council / United Kingdom
U01 AG016976 / AG / NIA NIH HHS / United States
P30 AG008051 / AG / NIA NIH HHS / United States
R01 AG017917 / AG / NIA NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
MC_U137686857 / / Medical Research Council / United Kingdom
G0902227 / / Medical Research Council / United Kingdom
089703 / / Wellcome Trust / United Kingdom
R01 HL105756 / HL / NHLBI NIH HHS / United States
P50 AG016573 / AG / NIA NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
R01 AG008122 / AG / NIA NIH HHS / United States
P50 AG005134 / AG / NIA NIH HHS / United States
R01 AG033193 / AG / NIA NIH HHS / United States
R01 NS080820 / NS / NINDS NIH HHS / United States
164 / / Alzheimer's Society / United Kingdom
G0601846 / / Medical Research Council / United Kingdom
R01 AG041797 / AG / NIA NIH HHS / United States
R01 AG041232 / AG / NIA NIH HHS / United States
P50 AG005138 / AG / NIA NIH HHS / United States
R01 AG037212 / AG / NIA NIH HHS / United States
/ / Arthritis Research UK / United Kingdom
R01 AG023629 / AG / NIA NIH HHS / United States
095317 / / Wellcome Trust / United Kingdom
100140 / / Wellcome Trust / United Kingdom
/ / Wellcome Trust / United Kingdom
MC_G1000734 / / Medical Research Council / United Kingdom
U01 AG049505 / AG / NIA NIH HHS / United States