Polygenic score analyses were conducted in PLINK using genotyped SNPs to test the hypothesis that multiple genes of small effect jointly contribute to TS and OCD susceptibility and to explore the genetic relationships between these disorders(25). Samples were divided into non-overlapping discovery and target samples (Supplementary Methods). For the primary OCD polygenic analysis, cases were restricted to subjects without known co-occurring TS/CT (OCD - TS/CT). SNPs with GWAS p-values passing pre-determined significance thresholds (p<0.01, 0.1, 0.2, 0.3, 0.4, and 0.5, respectively) in the discovery sample were extracted along with their risk alleles and odds ratios, and then LD pruned (r2<0.5). For each significance threshold, a quantitative aggregate risk score was calculated for each individual in the target sample, defined as the sum of the number of risk alleles present at each locus weighted by the log of the odds ratio for that locus estimated from the discovery sample. The relationship between aggregate risk score and case-control status in the target sample was examined at each significance threshold using logistic regression. The percentage of phenotypic variance explained by the aggregate risk score (Nagelkerke’s pseudo-R2) was estimated.
