By combining heterozygous damaging variants in the coding regions with associated heterozygous regulatory variants on the opposite allele (matched to genes by being an eQTL), we find 667 SNVs in possible instances of compound heterozygotes which directly affect the function of 93 genes. In these situations, binding site variants could inactivate gene expression in one allele, and a damaging mutation in the other allele might effectively completely disrupt gene function, thereby inactivating gene expression by regulatory/coding region compound heterozygosity. Furthermore, we find that, of the 40 genes in GM12878 that have heteroallelic expression and potential damaging mutations, half also have associated compound heterozygous mutations in a regulatory region (Supplemental Table S5).
