| Title: |
The trans-ancestral genomic architecture of glycemic traits |
| Authors: |
Chen, J; Spracklen, CN; Marenne, G; Varshney, A; Corbin, LJ; Luan, J; Willems, SM; Wu, Y; Zhang, X; Horikoshi, M; Boutin, TS; Mägi, R; Waage, J; Li-Gao, R; Chan, KHK; Yao, J; Anasanti, MD; Chu, AY; Claringbould, A; Heikkinen, J; incl. |
| Contributors: |
School of Medicine / Biomedicine; School of Medicine / Clinical Nutrition,School of Medicine / Clinical Medicine |
| Publisher Information: |
Springer Science and Business Media LLC |
| Publication Year: |
2022 |
| Collection: |
University of Eastern Finland: UEF Electronic Publications |
| 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. ; final draft ; peerReviewed |
| Document Type: |
article in journal/newspaper |
| File Description: |
840-860 |
| Language: |
English |
| ISSN: |
1061-4036 |
| Relation: |
Nature genetics; http://dx.doi.org/10.1038/s41588-021-00852-9; 53; https://erepo.uef.fi/handle/123456789/26896 |
| Availability: |
https://erepo.uef.fi/handle/123456789/26896 |
| Rights: |
In copyright 1.0 ; openAccess ; © The Authors, under exclusive licence to Springer Nature America, Inc. 2021 ; https://rightsstatements.org/page/InC/1.0/ |
| Accession Number: |
edsbas.D4F33DFD |
| Database: |
BASE |