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

Journal article

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 x 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 x 10(-9)) and 5' to the PICALM gene (rs3851179, P = 1.9 x 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 x 10(-10), odds ratio = 0.86; rs3851179, P = 1.3 x 10(-9), odds ratio = 0.86).

Authors: Harold, D; Abraham, R; Hollingworth, P; Sims, R; Gerrish, A

• Publication status: Published
• Journal: Nature genetics
• Volume: 41
• Issue: 10
• Pages: 1088-1093
• Publication date: 2009-10-01
• DOI: 10.1038/ng.440
• EISSN: 1546-1718
• ISSN: 1061-4036
• Language: English
• Keywords: Genome-Wide Association Study; Monomeric Clathrin Assembly Proteins; Polymorphism, Single Nucleotide; Genome, Human; Chromosomes, Human; Alzheimer Disease; Genetic Predisposition to Disease; Clusterin; Humans