Analysis of the GAsP dataset allows us to map out strategies for efforts focused on specific population centres in Asia as well as the generation of important tools that will increase our understanding of how genetic variants affect disease susceptibility and drug responses. The dataset improves the ability to filter out low-probability candidates for highly penetrant disorders, to identify putatively pathogenic variants that are found at high frequency in particular populations and improve the ability to infer pathogenicity of identified variants. The identification of novel homozygous PTVs in this study expands the catalogue of genes in which homozygous loss of function appears to be tolerated and, when combined with phenotype information, this will provide important biological insights into gene function. The ability to define gene function in humans through the study of the phenotypic effects of loss-of-function mutations is becoming an increasingly valuable approach51 and the study of additional variants and populations in which homozygosity occurs at high rates will add to the global resources for carrying out human knockout studies.
