Successful gene discovery by leveraging gene-level recurrent de novo variation in autism, where over 65 genes have now been identified (26, 28, 29), and the results presented here for OCD, strongly reinforce the value of continuing WES in larger cohorts of OCD parent- child trios. Our models predict that by increasing the sample size of this study to 500 trios, we will gain 9 additional high-confidence risk genes and 22 probable risk genes. Further increasing to 1,000 trios will yield a total of 40 high-confidence and 77 probable risk genes. Discovering risk genes will change the status quo in OCD genetics by allowing new studies in model systems (e.g. animal models, induced pluripotent stem cells) and network analyses. Such studies will provide insights into OCD pathophysiology that are critical prerequisites for the discovery of novel therapeutic targets to alleviate the suffering of those with OCD.
