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Nature genetics, 53 (6). pp. 840-860. ISSN 1061-4036 DOI: https://doi.org/10.1038/s41588-021-00852-9
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Abstract
Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10-8), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.
Item Type | Article |
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Faculty and Department | MRC Uganda > UG-HIV Care |
PubMed ID | 34059833 |
Elements ID | 161318 |
Official URL | http://dx.doi.org/10.1038/s41588-021-00852-9 |
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Filename: Chen-etal-2021-The-trans-ancestral-genomic-architecture.pdf
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