Table 1.
Enrichment of schizophrenia de novo variants in neurodevelopmental disorder (NDD) associated genes.
| NDD gene set (N genes) | Schizophrenia de novo variant enrichment | |||
|---|---|---|---|---|
| Mutation class | Obs/exp | P | Rate ratio (95% CI) | |
| PTV enriched genes (127) | PTVs | 20/3.41 | 2.14 × 10−8 | 4.89 (2.95, 7.67) |
| Missense (MPC > 2) | 6/4.57 | 0.47 | 1.32 (0.48, 2.95) | |
| PTV vs. missense (MPC > 2) | — | 0.006 | 3.70 (1.46, 9.41) | |
| Missense enriched genes (103) | PTVs | 4/2.94 | 0.79 | 1.09 (0.29, 2.80) |
| Missense (MPC > 2) | 14/7.85 | 0.04 | 1.86 (0.99, 3.23) | |
| Missense (MPC > 2) vs. PTV | — | 0.35 | 1.72 (0.56, 5.31) | |
| PTV + missense enriched genes (53) | PTVs | 7/1.64 | 0.0051 | 3.45 (1.38, 7.19) |
| Missense (MPC > 2) | 9/3.77 | 0.014 | 2.47 (1.11, 4.83) | |
| PTV vs. missense (MPC > 2) | — | 0.52 | 1.40 (0.51, 3.82) | |
Genes enriched for PTV or missense de novo variants in NDDs (significance threshold set at P < 2.5 × 10−6) were evaluated for enrichment of de novo variants in 3444 schizophrenia trios using a two-sample Poisson rate ratio test. P-values are uncorrected and two-tailed. NDD gene sets are defined as genes only associated with the given mutation class (i.e., excluding genes significant for the alternative mutation class) in the Deciphering Developmental Disorders study14. A Poisson regression model was used to evaluate differences between the rate of schizophrenia de novo PTVs and missense variants in NDD associated genes.