- Title
- The trans-ancestral genomic architecture of glycemic traits
- Creator
- Chen, Ji; Spracklen, Cassandra N.; Marenne, Gaëlle; Varshney, Arushi; Corbin, Laura J.; Luan, Jian'an; Willems, Sara M.; Wu, Ying; Zhang, Xiaoshuai; Horikoshi, Momoko; Boutin, Thibaud S.; Mägi, Reedik; Waage, Johannes; Li-Gao, Ruifang; Chan, Kei Hang Katie; Yao, Jie; Anasanti, Mila D.; Chu, Audrey Y.; Claringbould, Annique; Heikkinen, Jani; Wang, Carol A.; Pennell, Craig E.
- Relation
- Nature Genetics Vol. 53, Issue 6, p. 840-860
- Publisher Link
- http://dx.doi.org/10.1038/s41588-021-00852-9
- Publisher
- Nature Publishing
- Resource Type
- journal article
- Date
- 2021
- Description
- 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.
- Subject
- glycemic traits; type 2 diabetes; cardiometabolic health; glucose; trans-ancestry; diabetes pathophysiology; SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1464180
- Identifier
- uon:46927
- Identifier
- ISSN:1061-4036
- Language
- eng
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Goal 3: Good Health and Well-Being
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