We used Z-scores (correlated with Cochran’s Q statistic but provides directionality of the effect, Supplementary Methods) to assess heterogeneity between males and females. To obtain a Z-score, and corresponding p-values, for each tested variant, we calculated the differences in effect sizes (beta) between the sexes weighted by the square root of the sum of beta standard errors squared (equation 1). Equation 1Z−score=Betafemale−BetamaleSEfemale2+SEmale2 We define SNPs with Sexually Differentiated Effect (SDEs) as those variants at the extreme ends of the distribution with an absolute value of the Z-score greater than 3 (∣Z-score∣>3), which is roughly equivalent to p<10−3, and represents 0.3% of all tested SNPs.
