The primary limitation of this study relates to sample size. While our study represents the largest genetic sample of either disorder studied to date, the total sample of 3013 cases and 5957 controls has 67% power to detect a disease variant with an odds ratio of 1.25 (assuming risk allele frequency is 20% in the general population), and only 25% power to detect a variant with an odds ratio of 1.20. Recent studies of other psychiatric disorders with evidence of genetic overlap have required substantially larger sample sizes in order to detect individual variants that contribute to both disorders (32, 33). Therefore, caution is necessary when drawing conclusions about the genetic architecture of TS and OCD based exclusively on the results of the combined GWAS. However, we have more confidence in our interpretation of the polygenic analyses, where demonstrated significant differences between the aggregate polygenic risk for the TS/OCD phenotypes despite comparatively small sample sizes. Of note, aggregate polygenic signals have been successfully detected with a comparable number of subjects in other cross-disorder studies as well (32, 33).
