To explore the influence of phenotype co-morbidity on polygenic risk score prediction, an additional “All OCD” discovery sample was created which included the primary OCD discovery sample plus 345 additional cases with OCD + TS/CT. As expected, the polygenic score using risk alleles derived from this discovery sample predicted case-control status in the OCD target sample (p=2.3×10−3) (Figure 3). However, the proportion of variance explained by the “All OCD” risk score was significantly attenuated compared to the risk score derived from the primary “OCD - TS/CT” discovery sample, despite the 30% increase in sample size (“OCD - TS/CT”, n=1154, R2=3.2%; “All OCD”, n=1499, R2=2.1%; permutation p=0.01, Figures 3 and S9).
