Common genetic variation – variants shared among many individuals in a population and most frequently SNPs – has been found to play a role in liability for most psychiatric disorders, including OCD. Open questions remain about the impact on risk due to common variation, including how much of the heritability of OCD it accounts for and how it is partitioned across the frequency spectrum of alleles. These are important questions for a variety of reasons. For example, both schizophrenia and autism spectrum disorder demonstrate high heritability (32, 33) and much of it traces to common genetic variation. Yet rare variation with a damaging impact on gene function, especially de novo variation, plays a larger role in overall autism spectrum disorder risk than in overall schizophrenia risk (32, 34, 35); e.g., in Singh et al. (35), de novo protein truncating variants were found to be fourfold more common in individuals with autism than schizophrenia when they evaluated evolutionarily-constrained genes. This difference is critical for clinical genetics, genetic counseling, and possibly treatment. It also could be relevant for disentangling evolutionary processes underlying
