Homozygous loss-of-function alleles found in humans give us the opportunity to assess the phenotypic effect of specific gene loss and can provide important information about opportunities for treating disease46,47. To assess the contents of our dataset, we examined high-confidence protein-truncating variants (PTVs). We found 17,566 PTVs with at least 1 PTV in approximately 43% of all protein-coding genes (n = 8,766; Fig. 4c). Among the PTVs, most were heterozygous variants unique to our dataset (n = 8,799; Fig. 4d), similar to the PTV data from ExAC25 (67% singletons). A smaller number were homozygous and had been reported in gnomAD, dbSNP or 1000 Genomes Project (n = 856). In addition, within our dataset were 121 homozygous PTVs that have not previously been reported (Supplementary Table 5). These novel homozygous PTVs were mostly found in groups with high IBD scores such as the Jarawa and Onge from the Andaman Islands (Fig. 4e). The novel homozygous PTVs include an allele of the ABCA7 gene, Q2010*, that is found in only the Aeta population (Fig. 4f). Heterozygosity for loss-of-function alleles of ABCA7 has been shown to increase susceptibility to Alzheimer’s disease in European populations48.
