Abstract
BackgroundThe association between BIN1 rs744373 variant and Alzheimer’s disease (AD) had been identified by genome-wide association studies (GWASs) as well as candidate gene studies in Caucasian populations. But in East Asian populations, both positive and negative results had been identified by association studies. Considering the smaller sample sizes of the studies in East Asian, we believe that the results did not have enough statistical power.ResultsWe conducted a meta-analysis with 71,168 samples (22,395 AD cases and 48,773 controls, from 37 studies of 19 articles). Based on the additive model, we observed significant genetic heterogeneities in pooled populations as well as Caucasians and East Asians. We identified a significant association between rs744373 polymorphism with AD in pooled populations (P = 5 × 10− 07, odds ratio (OR) = 1.12, and 95% confidence interval (CI) 1.07–1.17) and in Caucasian populations (P = 3.38 × 10− 08, OR = 1.16, 95% CI 1.10–1.22). But in the East Asian populations, the association was not identified (P = 0.393, OR = 1.057, and 95% CI 0.95–1.15). Besides, the regression analysis suggested no significant publication bias. The results for sensitivity analysis as well as meta-analysis under the dominant model and recessive model remained consistent, which demonstrated the reliability of our finding.ConclusionsThe large-scale meta-analysis highlighted the significant association between rs744373 polymorphism and AD risk in Caucasian populations but not in the East Asian populations.
Highlights
Alzheimer’s disease (AD) is the preeminent cause for dementia in the elderly and causes 50–75% dementia types [1,2,3]
Genetic model Since not all studies provided exact genotype numbers, we investigated the association between rs744373 polymorphism and AD risk in this meta-analysis primarily using the additive genetic model
We further excluded 24 articles because they did not investigate the association between rs744373 polymorphism and AD or not provide sufficient data
Summary
Alzheimer’s disease (AD) is the preeminent cause for dementia in the elderly and causes 50–75% dementia types [1,2,3]. In the populations of Caucasian ancestry, large-scale genome-wide association studies (GWASs) have identified some common genetic risk factors for AD [4]. In 2013, we conducted a meta-analysis using all currently available samples (2022 AD cases and 4209 controls) and the results were significant (P = 1.19 × 10 − 02, 7.08 × 10 − 03 and 5.75 × 10 − 03 for the dominant model, recessive model and additive model) [30]. The association between BIN1 rs744373 variant and Alzheimer’s disease (AD) had been identified by genome-wide association studies (GWASs) as well as candidate gene studies in Caucasian populations. In East Asian populations, both positive and negative results had been identified by association studies. Considering the smaller sample sizes of the studies in East Asian, we believe that the results did not have enough statistical power
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