polymorphisms with increased
brain expression confer higher risk for Alzheimer’s disease. (A) The odds ratios and 95% confidence intervals (95% CI) were calculated by binary logistic regression using genotype of 5 common VAMP1 polymorphisms, age, sex and APOE ε4 allele as predictive variables for diagnosis were performed following additive, dominant and recessive models; the best model (lowest p-value) for each polymorphism is shown plotted on the y-axis. A significant protective effect of rs2072376 can be seen (OR = 0.88, p = 0.03). The β-coefficients (+/- standard error of the mean) for the same polymorphisms with cerebellar VAMP1 mRNA expression are plotted on the x-axis. The polymorphisms associated with increased VAMP1 brain expression (rs7390 and rs2240867) have higher ORs for Alzheimer’s disease susceptibility than those associated with decreased expression. (B) Meta analyses across subpopulations (Jacksonville; JS, Rochester; RS, Autopsy-confirmed; AUT) for the rs2072376 polymorphism shows different effect sizes across each population. The population meta-analysis for all samples was not significant (p = 0.62). (C) The odds ratios and 95% confidence intervals (95% CI) were calculated for 4 rare VAMP1 polymorphisms (adjusted for age, sex and APOE ε4 allele). A significant association was observed for rs74056956 and rs71548434. Meta analyses across subpopulations for rs74056956 (D) and (E) rs71548434 show different effect sizes across each population and were not significant (p = 0.80 and 0.10, respectively). The log10 of the odds ratio and 95% CI are plotted on the x-axis for better visualization. The populations in which the genotypes deviated from Hardy Weinberg equilibrium are marked by an asterisk.