Analyzing 54,936 Samples Supports the Association Between CD2AP rs9349407 Polymorphism and Alzheimer's Disease Susceptibility

The CD2-associated protein (CD2AP) rs9349407 polymorphism was first identified to be significantly associated with Alzheimer's disease (AD) in European ancestry by genome-wide association studies (GWAS). However, the following studies reported no association in Chinese, Japanese, African-American, Canadian, and European populations. We think that these negative results may have been caused by either relatively small sample sizes compared with those used for the previous GWAS in European ancestry or the genetic heterogeneity of the rs9349407 polymorphism in different populations. Here, we reevaluated this association using the relatively large-scale samples from 15 previous studies (N=54,936; 23,777 cases and 31,159 controls) by searching the PubMed, AlzGene, and Google Scholar databases. Using an additive genetic model, we did not identify a significant heterogeneity among the 15 studies. Using meta-analysis, we observed a significant association between the rs9349407 polymorphism and AD with P-8.78E-07, odds ratio (OR)-1.08, 95 % confidence interval (CI) 1.05-1.12. To our knowledge, this is the first meta-analysis to investigate the association between rs9349407 polymorphism and AD in East Asian, American, Canadian, and European populations. Our analysis further supports previous findings that the CD2AP rs9349407 polymorphism contributes to AD susceptibility. We believe that our findings will be very useful for future genetic studies on AD.