Table 4.
Burden of de novo variants in pediatric-onset PAH (n = 124 child-parent trios)
| Variant type* | Observed | Expected by chance | Enrichment | p value | Estimated # of risk variants | |
|---|---|---|---|---|---|---|
|
All genes (18,939 genes) |
SYN | 42 | 38.3 | 1.1 | 0.51 | N/A |
| LGD | 14 | 11.8 | 1.2 | 0.46 | N/A | |
| MIS | 93 | 84.7 | 1.1 | 0.36 | N/A | |
| D-Mis | 30 | 17.3 | 1.73 | 0.005 | N/A | |
| LGD + D-Mis | 44 | 28.9 | 1.52 | 0.009 | 15 | |
|
HLE or HHE** (5756 genes) |
SYN | 18 | 14.01 | 1.28 | 0.28 | N/A |
| LGD | 10 | 4.69 | 2.13 | 0.03 | N/A | |
| MIS | 40 | 31.68 | 1.26 | 0.15 | N/A | |
| D-Mis | 19 | 7.25 | 2.62 | 2.0e−4 | 12 | |
| LGD + D-Mis | 29 | 11.85 | 2.45 | 2.5e−5 | 17 |
* SYN, synonymous; LGD, likely gene-disrupting; MIS, missense; D-Mis, deleterious missense based on REVEL > 0.5
**HLE, high lung expression (murine E16.5 lung stromal cells); HHE, high heart expression (murine E14.5 heart)