Abstract
Recent genome-wide association studies (GWAS) have discovered several Alzheimer disease (AD) susceptibility loci. However, the identified susceptibility loci are substantially inconsistent across GWAS. We aimed to investigate the association of top associated variants in GWAS with AD in Korean population. We selected 86 single-nucleotide polymorphisms (SNPs) selected from 12 genes (ABCA7, APOE, BIN1, CD2AP, CD33, CLU, CR1, EPHA1, LRAT, MS4A6A, PCDH11X, and PICALM) and genotyped in 290 AD cases and 554 unrelated controls from the same region. Three SNPs [rs429358 in APOE: odds ratio (OR)=4.24, 95% confidence interval (CI)=3.01-5.96, P=1.23×10; rs2075650 in APOE: OR=3.57, 95% CI=2.51-5.06, P=1.23×10; and rs677909 in PICALM: OR=0.63, 95% CI=0.49-0.81, P=0.00036, log additive model] were significantly associated with AD susceptibility after correction for multiple testing. Six additional PICALM SNPs, 3 ABCA7 SNPs, and 1 APOE, CD33, and BIN1 SNPs each had significant uncorrected P values. There was no significant association for age at onset of AD. Our results confirm the association of PICALM gene (encoding phosphatidylinositol-binding protein) in addition to APOE gene with AD susceptibility in Korean population but did not show significant associations of other susceptibility loci with AD.
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