An Updated Analysis with 85,939 Samples Confirms the Association Between CR1 rs6656401 Polymorphism and Alzheimer's Disease

The complement receptor 1 (CR1) rs6656401 polymorphism was first identified to be associated with Alzheimer's disease (AD) in European ancestry. However, the following studies reported weak or no significant association in Chinese, Japanese, Korean, African-American, Polish, and Canadian populations. We think that these negative results may have been caused by either relatively small sample sizes compared with those used for the previous genome-wide association studies (GWAS) in European ancestry or the genetic heterogeneity of the rs6656401 polymorphism in different populations. Here, we reevaluated this association using the relatively large-scale samples from previous 24 studies (N = 85,939, 30,100 cases and 55,839 controls) by searching the PubMed, AlzGene, and Google Scholar databases. Using additive model, we did not identify significant heterogeneity among the 24 studies. We observed significant association between the rs6656401 polymorphism and AD in pooled populations (P = 1.82E-26, odds ratio (OR) = 1.18, 95 % confidence interval (CI) 1.15-1.22). In subgroup analysis, we identified significant results in East Asian population with P = 5.00E-04, OR = 1.31, 95 % CI 1.13-1.52. To our knowledge, this is the first meta-analysis to investigate the association between rs6656401 polymorphism and AD in East Asian, African-American, Canadian, and European populations. Our analysis further supports previous findings that the CR1 rs6656401 polymorphism contributes to AD susceptibility. We believe that our findings will be very useful for future genetic studies on AD.