Study design: In total 16 studies containing more than 11000 individuals of various ethnicities were selected for the analyses. For 11 case-control studies, odds ratio (OR) was employed to evaluate the risk of late AAM for each study, using homozygote at the wild-type allele as a control group. For the 5 studies with continuous outcomes, the effect size was estimated using the Hedges’ adjusted g, which is calculated based on the standardized mean difference between groups of subjects with early and late AAM.