Next, we carried out meta-analysis using a weighted z-score method, which accounts for the direction of association relative to a consistent reference allele. In this method, P values for each study are first converted to z scores. Then, a weighted sum of z scores is calculated where each statistic is weighted by the square root of the sample size for each study. The resulting sum is divided by the square root of the total sample size to obtain an overall z statistic, which can be used to evaluate the overall evidence for association. The method takes direction of effect across studies into account by reversing the sign of the z score for a study if the effect is in the opposite direction. We obtained similar results when we analyzed each cohort using a uniform protocol (which involved a quantile transformation to approximate normality and adjusting for age and age2 in men and women separately) and combined the results using the regression coefficients and standard errors estimated from each study (Supplementary Fig. 2; Pearson correlation r = 0.91). Both meta-analysis procedures
