We used PLINK to perform a genotype-sex (GxS) interaction analysis, with principal components as covariates, in each of the individual datasets. We then used METAL to meta-analyze the interaction results. A sex-stratified analysis followed by difference test (Z-score, see below) is equivalent to a formal test for genotype-sex interaction when there is no interaction between covariates and the strata, and the trait variance are equivalent in the two strata. However, different information can be gained from both types of analyses. An interaction test on a combined sample is powered to detect a difference between the sexes in genetic risk and needed to determine whether differences in effect sizes are statistically different between the sexes. On the other hand, a stratified analysis is required in order to characterize the effect size itself, and the direction of effect within each sex.
