Two separate statistical approaches were used to determine the significance of the observed differences in polygenic risk score prediction between discovery samples. First, permutation testing was conducted to derive an empirical significance of the magnitude of change in R2 between polygenic risk scores derived from the OCD - TS/CT discovery sample compared to those derived from the “All OCD” sample (OCD +/− TS/CT). Second, risk alleles from each discovery sample were used to calculate the difference in polygenic risk scores between the transmitted (case) alleles and the untransmitted (pseudo-control) alleles in the OCD Trio target sample. The degree of risk score elevation (Risk Scoretransmitted − Risk Scoreuntransmitted) was then standardized ([RStrans−RSuntrans]/RSuntrans), and compared between different discovery samples using two-sided paired t-tests. See Supplementary Methods for further details of both approaches.
