Analyzing Large-Scale Samples Confirms the Association Between the ABCA7 rs3764650 Polymorphism and Alzheimer’s Disease Susceptibility

Abstract

Large-scale genome-wide association studies (GWAS) have revealed that the ABCA7 rs3764650 polymorphism (or its proxies, namely rs115550680, rs3752246, and rs4147929) is associated with Alzheimer's disease (AD) susceptibility in individuals of Caucasian ancestry. The following studies have investigated this finding in Chinese (N = 633 and N = 1,224), Japanese (N = 1,735), Korean (N = 844), African American (N = 5,896), and Canadian (N = 1,104) populations. However, these studies reported a weak or negligible association. We hypothesized that these negative results may have been caused by either relatively small sample sizes compared with those used for the previous GWAS in individuals of Caucasian ancestry or the genetic heterogeneity of the rs3764650 polymorphism (or its proxies) in different populations. Here, we reevaluated the association between rs3764650 and AD using large-scale samples from 18 previous studies (N = 79,381-30,590 cases and 48,791 controls) by searching PubMed, AlzGene, and Google Scholar databases. Using allele, dominant, recessive, and additive models, we did not identify significant heterogeneity among the 18 studies. We observed a significant association between rs3764650 and AD using the allele (P = 1.76E - 26, odds ratio (OR) = 1.21, 95 % confidence interval (CI) 1.17-1.26), dominant (P = 4.00E - 04, OR = 1.17, 95 % CI 1.07-1.28), recessive (P = 3.00E - 03, OR = 1.43, 95 % CI 1.13-1.81), and additive models (P = 3.00E - 03, OR = 1.49, 95 % CI 1.16-1.91). Collectively, our analysis further supports previous findings that the ABCA7 rs3764650 polymorphism is associated with AD susceptibility. We believe that our findings will be very useful for future genetic studies on AD.