Figure 3.
Enrichments of shet in known haploinsufficient disease genes of high confidence (ClinGen Dosage Sensitivity Project). In (N=127) autosomal genes, we annotate the shet scores of genes associated with each disease category and classification. Higher shet values are associated with [a] earlier age of onset (Mann-Whitney U p=1.46 ×10−2), [b] a larger fraction of de novo variants (p=8×10−5), [c] high or unspecified penetrance (p=1.79 ×10−2) and [d] increased phenotypic severity (p=4.87×10−3). Box plots range from 25th–75th percentile values and whiskers include 1.5 times the interquartile range. [e] Genes with the 10% highest shet values are also similarly enriched with more severe clinical annotations.