On the other end of the spectrum, relatively rare variants (SNPs with frequencies less than 5%) are predicted to account for 21% of the heritability in Tourette syndrome but none of the heritability of OCD (40). Still, for Tourette syndrome, only a single very rare dominant mutation has been identified in one family (41). For other disorders, ranging from major depression to substance abuse and anxiety disorders, for which there is strong evidence of heritable polygenic risk, we lack significant evidence of rare large-effect-size variant contributions, consistent with differences in genetic architecture across psychiatric diseases, although study design and small cohort sizes may also contribute.
