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

Mahajan, Anubha; Spracklen, Cassandra N; Zhang, Weihua; Ng, Maggie CY; Petty, Lauren E; Kitajima, Hidetoshi; Yu, Grace Z; ... Morris, Andrew P; + view all (2022) Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation. Nature Genetics , 54 (5) pp. 560-572. 10.1038/s41588-022-01058-3. Green open access

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Abstract

We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 × 10−9), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations 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 the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background.

Type: Article
Title: Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41588-022-01058-3
Publisher version: https://doi.org/10.1038/s41588-022-01058-3
Language: English
Additional information: This version is the author accepted manuscript. - For the purpose of Open Access, the authors have applied a CC-BY public copyright licence to any Author Accepted Manuscript version arising from this submission.
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
URI: https://discovery.ucl.ac.uk/id/eprint/10155438
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