Trans-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation

<jats:title>ABSTRACT</jats:title><jats:p>We assembled an ancestrally diverse collection of genome-wide association studies of type 2 diabetes (T2D) in 180,834 cases and 1,159,055 controls (48.9% non-European descent). We identified 277 loci at genome-wide significance (<jats:italic>p</jats:italic><5×10<jats:sup>-8</jats:sup>), including 237 attaining a more stringent trans-ancestry threshold (<jats:italic>p</jats:italic><5×10<jats:sup>-9</jats:sup>), which were delineated to 338 distinct association signals. Trans-ancestry meta-regression offered substantial enhancements to fine-mapping, with 58.6% of associations more precisely localised due to population diversity, and 54.4% of signals resolved to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying foundations for functional investigations. Trans-ancestry genetic risk scores enhanced transferability across diverse populations, providing a step towards more effective clinical translation to improve global health.</jats:p>