Similar success evades genetic analysis of other psychiatric disorders, for which we have very few large-effect genes that have been independently replicated. Work on SCZ is closest to identifying mutations in specific genes. Initial studies identified increased rates of de novo mutations (38), observing that the number of loss-of-function events in cases is almost three times higher than in control family trios (8.7% compared to 2.9%) (39). However, studies with larger sample sizes (18, 19) failed to confirm an overall enrichment of de novo mutations, and identification of individual susceptibility genes via WES has eluded researchers. Enrichment of mutations was found, but only when analysis was restricted to sets of hypothesis-driven candidate genes (19).
