Appendix 1—table 1. Summary counts for LOF and synonymous mutations by pedigree study or subsample.
Studies can differ in the amount of the genome queried for LOF mutations. The number of probands is obtained as the number of unique Proband IDs with at least one reported de novo mutation (of any kind). For two studies where this information was not available, the number of probands was obtained from the text. The probability that an LOF mutation is under hs > 10% is calculated using the area under the DFE for hs > 10%. The probability that an LOF mutation under hs > 10% is causal is calculated as 1 – the ratio of the probability that an LOF mutation is under hs > 10% in a sample ascertained for a disease and the probability that an LOF mutation is under hs > 10% in the population (19.8%), and set to zero if negative.
| Sample | # Affected Individuals | Average number of Synonymous DNMs in an individual | Average number of LOF DNMsin an individual | Probability LOF has hs > 10% | Probability LOF causal if hs > 10% |
|---|---|---|---|---|---|
| Developmental disorders (2623 DNMs in 23,902 trios) | 23,902 | 0.38 | 0.11 | 0.50 | 0.60 |
| Congenital heart disease (192 DNMs in 1785 trios) | 1785 | 0.39 | 0.11 | 0.36 | 0.45 |
| Severe epilepsy (58 DNMs in 406 trios) | 406 | 0.35 | 0.14 | 0.46 | 0.57 |
| Autism (560 DNMs in 5297 trios) | 5297 | 0.35 | 0.11 | 0.35 | 0.43 |
| Schizophrenia (263 DNMs in 2381 trios) | 2381 | 0.24 | 0.11 | 0.28 | 0.28 |
| Tourette syndrome/OCD (62 DNMs in 436 trios) | 436 | 0.39 | 0.14 | 0.25 | 0.19 |
| DDD (445 DNMs in 4336 affected males) | 4336 | 0.41 | 0.10 | 0.49 | 0.59 |
| DDD (462 DNMs in 3411 affected females) | 3411 | 0.39 | 0.14 | 0.52 | 0.62 |
| Simons Simplex (117 DNMs in 1623 affected males) | 1623 | 0.25 | 0.07 | 0.35 | 0.43 |
| Simons Simplex (21 DNMs in 249 affected females) | 249 | 0.24 | 0.08 | 0.58 | 0.66 |
| MSSNG Simplex (38 DNMs in 531 affected males) | 531 | 0.32 | 0.07 | 0.40 | 0.51 |
| MSSNG Simplex (7 DNMs in 153 affected females) | 153 | 0.27 | 0.05 | 0.58 | 0.66 |
| SPARK (76 DNMs in 279 affected males) | 279 | 0.47 | 0.27 | 0.29 | 0.32 |
| SPARK (12 DNMs in 68 affected females) | 68 | 0.44 | 0.18 | 0.47 | 0.58 |
| MSSNG multiplex (35 DNMs in 491 affected males) | 491 | 0.36 | 0.07 | 0.19 | 0.00 |
| MSSNG multiplex (15 DNMs in 175 affected females) | 175 | 0.38 | 0.09 | 0.13 | 0.00 |