also coded in an identical manner. In each replication attempt, only the identical phenotype was tested in the replication cohort (e.g., for a variant that was GWS for one criterion but not others, only association with that criterion was tested in the replication samples). Due to the small sizes of the individual AA and EA subsets of the replication datasets, only the AA subsample of SAGE (SAGE-AA), EA subsample of SAGE (SAGE-EA), AA subsample of Yale-Penn (Yale-Penn-AA), and EA subsample of OZALC (OZALC-EA) were included as replication samples. Empirical kinships were estimated from genome-wide genotypic data using the “vcf2kinship” tool as implemented in RVTESTS, then mixed models adjusting for empirical kinships were fitted to the data using RVTESTS 45. For both SAGE-AA and SAGE-EA, sex and birth cohort (as defined in COGA) were used as covariates, while for OZALC-EA and Yale-Penn-AA, sex and age were used, as in publications of the parent studies. In addition, the first three PCs were included in all replication analyses.
