Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease

D Harold, R Abraham, P Hollingworth, R Sims… - Nature …, 2009 - nature.com
D Harold, R Abraham, P Hollingworth, R Sims, A Gerrish, ML Hamshere, JS Pahwa…
Nature genetics, 2009nature.com
We undertook a two-stage genome-wide association study (GWAS) of Alzheimer's disease
(AD) involving over 16,000 individuals, the most powerful AD GWAS to date. In stage 1
(3,941 cases and 7,848 controls), we replicated the established association with the
apolipoprotein E (APOE) locus (most significant SNP, rs2075650, P= 1.8× 10− 157) and
observed genome-wide significant association with SNPs at two loci not previously
associated with the disease: at the CLU (also known as APOJ) gene (rs11136000, P= 1.4× …
Abstract
We undertook a two-stage genome-wide association study (GWAS) of Alzheimer's disease (AD) involving over 16,000 individuals, the most powerful AD GWAS to date. In stage 1 (3,941 cases and 7,848 controls), we replicated the established association with the apolipoprotein E (APOE) locus (most significant SNP, rs2075650, P = 1.8 × 10−157) and observed genome-wide significant association with SNPs at two loci not previously associated with the disease: at the CLU (also known as APOJ) gene (rs11136000, P = 1.4 × 10−9) and 5′ to the PICALM gene (rs3851179, P = 1.9 × 10−8). These associations were replicated in stage 2 (2,023 cases and 2,340 controls), producing compelling evidence for association with Alzheimer's disease in the combined dataset (rs11136000, P = 8.5 × 10−10, odds ratio = 0.86; rs3851179, P = 1.3 × 10−9, odds ratio = 0.86).
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