In the association analysis of schizophrenia the odds ratio of 56372821(CI95%) was OR=0.9 (0.81-0.99). When excluding all individuals with CUD, among cases and controls (1,727 cases and 23,033 controls) the odds ratio of rs56372821(CI95%) was OR=0.97 (0.87-1.09). To evaluate whether this change in the odds ratio is due to removal of individuals with CUD (554 cases and 101 control with CUD removed) or due to reduction in sample size, a null distribution of OR's was generated by randomly removing 554 individuals among schizophrenia cases and 101 individuals among controls (removing a total of 655 individuals). This permutation of sample exlcusion was done 9,999 times to generate the null distribution of the odds ratio for rs56372821. To obtain a two-sided P-value, the observed ln(ORrs56372821)=−0.03 was mirrored around the mean ln(ORrs56372821) of the null distribution, as shown in Supplementary Figure 1. Removal of individuals with CUD (554 SZ cases and 101 controls) changed the OR of rs56372821 significantly, compared to random removal of the same number of schizophrina cases and controls (Ptwo-sided=0.0027), producing a significant increase of ORrs56372821 compared to random removal (Pone-sided=0.0015).
