found a statistically significant increased rate of de novo LGD variants in OCD cases, confirming our hypothesis (rate ratio [RR] 1.93, 95% Confidence Interval [CI] 1.19–3.09, p=0.01). Furthermore, de novo missense variants predicted to be damaging by PolyPhen2 (Mis-D; Polyphen2 HDIV score >0.957) were also over-represented in OCD probands (RR 1.43, CI 1.13–1.80, p=0.006). Taken together, damaging de novo coding variants (LGD and Mis-D) occur more often in OCD probands versus controls (RR 1.52, CI 1.23–1.86, p=0.0005). We did not detect a difference in mutation rates for de novo synonymous variants (RR 0.99, CI 0.75–1.31, p=0.5) (Table 1, Figure 2A, Table S2). We did not detect a difference in mutation rates for any class of inherited variants (Tables S3–S4).
