In contrast, genetic research into several other neuropsychiatric disorders has seen significant advancement in recent years. This progress is partly attributable to increasing attention toward the contribution of rare genetic sequence variation, especially de novo variants which arise spontaneously in parental germ cells or in a zygote shortly after conception. This approach has shown great success for systematic risk gene discovery in other genetically complex neuropsychiatric disorders (21–25), particularly autism spectrum disorders (26–29). While an individual rare variant is unlikely to explain a sizeable fraction of disease risk in the context of a heterogeneous genetic architecture, concurrent investigations of multiple genes implicated by rare sequence and structural variation highlight convergence toward a limited number of important underlying biological mechanisms (30). Therefore, there is a proven and reliable approach toward risk gene discovery in complex neuropsychiatric disorders that has yet to be fully leveraged in OCD.
