BIN1 rs744373 Variant Is Significantly Associated with Alzheimer's Disease in Caucasian but Not East Asian Populations

Genome-wide Association studies (GWAS) and candidate gene studies have identified the association between BIN1 rs744373 variant and Alzheimer's disease (AD) in Caucasian populations. Recently, a number of studies investigated the association between BIN1 rs744373 and AD in Asian populations. However, both positive and negative results have been identified. We consider that the relatively small sample sizes may lead to the lower statistical power. Here, we selected 71,168 samples (22,395 AD cases and 48,773 controls) from 19 articles containing 38 studies and reinvestigated this association using meta-analysis method. We observed a significant genetic heterogeneity and identified a significant association between rs744373 polymorphism with AD in pooled populations (P = 5 x 10(-07), OR = 1.12, and 95% confidence interval (CI) 1.07-1.17). In subgroup analysis, we not only identified significant genetic heterogeneity in East Asian but also in Caucasian. The subgroup meta-analysis only revealed significant association between rs744373 polymorphism with AD in the Caucasian populations (P = 3.38 x 10(-08), OR = 1.16, 95% CI 1.10-1.22), but not in the East Asian populations (P = 0.393, OR = 1.057, and 95% CI 0.95-1.15). The regression analysis suggested no significant publication bias. In summary, this large-scale meta-analysis highlighted the significant association between rs744373 polymorphism and AD in Caucasian populations but not in the East Asian populations.