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.
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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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