Exome sequencing of 44,028 British South Asians uncovers thousands of rare knockouts and novel gene–phenotype links
Sequencing 44,028 British Pakistani/Bangladeshi volunteers with high autozygosity creates a large South Asian exome resource linked to health records, identifying ~4.7 million variants, 2,991 genes with rare biallelic loss-of-function genotypes (546 novel), and over 100 newly linked gene–phenotype associations. Meta-analysis with UK Biobank reinforced cardiometabolic signals, and analyses of recessive burdens and human knockouts illustrate how knockout genotypes can inform drug target safety and efficacy, aiding disease interpretation and guiding drug development. Data and code are publicly available via cloud and GitHub.
