We performed a PheWAS using exome sequences of 269,171 UKB participants of European ancestry combined with records of 18,780 phenotypes, followed by a pan-ancestry analysis that incorporated an additional 11,933 UKB participants of African, East Asian and South Asian ancestries. In total, we identified 46,837 variant-level and 1,703 gene-level statistically significant relationships. Many associations were previously known, but others were either new or associated with phenotype expansions. We also found that these associations were significantly enriched for targets of US Food and Drug Administration (FDA)-approved drugs, reinforcing the importance of human genetics in target identification. When followed up with functional investigation to understand biological mechanisms, these results can help to improve the efficiency of pharmaceutical pipelines, contribute towards safety assessments and reveal repositioning opportunities7,42.
