Association of PICALM Gene with Late-Onset Alzheimer's Disease in Korean Population (P05.073)

Abstract

Objective: We aimed to investigate the association of top associated variants in GWAS with Alzheimer9s disease (AD) in Korean population. Background AD is the most common cause of neurodegenerative adult-onset dementia. Recent genome-wide association studies (GWAS) have discovered several AD susceptibility loci. However, the identified susceptibility loci are substantially inconsistent across GWAS of Caucasian population. Design/Methods: We selected single nucleotide polymorphisms (SNPs) selected from 12 genes (ABCA7, APOE, BIN1, CD2AP, CD33, CLU, CR1, EPHA1, LRAT, MS4A6A, PCDH11X, and PICALM) that had genome-wide significance in recent GWAS and additional tag SNPs in each gene using the HapMap Asian (CHB and JPT) samples, and genotyped in 290 AD cases from all regions of South Korea and 554 unrelated controls from the same region. All subjects were Korean population. Case-control analyses were performed to study association with AD susceptibility, while cases-only analyses were used to study association with age at onset. Results: Three SNPs (rs429358 in APOE, rs2075650 in APOE, and rs677909 in PICALM) were associated with AD susceptibility after correction for multiple testing. After adjustment of APOE gene, only PICALM SNP rs677909 remained significant after Bonferroni correction (OR = 0.629, 95% CI = 0.488 – 0.81, uncorrected p = 0.0003, log additive model). However, 6 additional PICALM SNPs, 3 ABCA7 SNPs, and one APOE, CD33, and BIN1 SNPs each had significant uncorrected p values. There was no significant association for age at onset after correction for multiple testing. Conclusions: Our results confirm the association of PICALM gene (encoding phosphatidylinositol-binding protein) in addition to APOE gene with AD susceptibility in Korean population but show limited association of other susceptibility loci with AD. All AD susceptibility loci were not associated with age at onset of AD in Korean population. Supported by: A grant of the Korea Healthcare technology R & D Project, Ministry of Health and Welfare, Republic of Korea (A092042). This study was also partially supported by a grant of the Korea Healthcare technology R & D Project, Ministry of Health and Welfare, Republic of Korea (A102065). Disclosure: Dr. Chung has nothing to disclose. Dr. Lee has nothing to disclose. Dr. Kim has nothing to disclose. Dr. You has nothing to disclose. Dr. Kim has nothing to disclose. Dr. Koh has nothing to disclose.