TABLE 2.
Top six gene-set clusters for truncating ultra-rare variant burden analyses in CHD using Gene Ontology (GO)/pathways and Mouse Phenotype Ontology (MPO), and restricting to constrained genes.
| Gene-set clusters | Observed truncating variants in constrained genes (o/e score in gnomAD < 0.35) | P-value | Resampling based FDR |
| GO/pathways | |||
| VEGF signaling and blood vessel development | 8 | 5.39×10−13 | 0 |
| Ion antiporter activity | 5 | 0.0005 | 0.9564 |
| Planar cell polarity pathway involved in neural tube closure | 3 | 0.0013 | 0.9564 |
| Positive regulation of vascular associated smooth muscle cell migration | 4 | 0.0017 | 0.9564 |
| Peptidyl-tyrosine autophorphorylation | 5 | 0.0027 | 0.9564 |
| Protein quality control for misfolded or incompletely synthesized proteins | 3 | 0.0029 | 0.9564 |
| MPO | |||
| Abnormal lymphangiogenesis | 7 | 9.64×10−11 | 0.0080 |
| Abnormal cranial neural crest cell morphology | 3 | 0.0010 | 0.9605 |
| Neuronal cytoplasmic inclusions | 2 | 0.0022 | 0.9605 |
| Absent pharyngeal arches | 4 | 0.0031 | 0.9605 |
| Abnormal CD5-positive T cell number | 2 | 0.0036 | 0.9605 |
| Cochlear ganglion degeneration | 4 | 0.0037 | 0.9605 |