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Dokumenttyp:
Article; Journal Article; Meta-Analysis
Autor(en):
Mahajan, Anubha; Spracklen, Cassandra N; Zhang, Weihua; Ng, Maggie C Y; Petty, Lauren E; Kitajima, Hidetoshi; Yu, Grace Z; Rüeger, Sina; Speidel, Leo; Kim, Young Jin; Horikoshi, Momoko; Mercader, Josep M; Taliun, Daniel; Moon, Sanghoon; Kwak, Soo-Heon; Robertson, Neil R; Rayner, Nigel W; Loh, Marie; Kim, Bong-Jo; Chiou, Joshua; Miguel-Escalada, Irene; Della Briotta Parolo, Pietro; Lin, Kuang; Bragg, Fiona; Preuss, Michael H; Takeuchi, Fumihiko; Nano, Jana; Guo, Xiuqing; Lamri, Amel; Nakatochi, M...     »
Titel:
Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation.
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.
Zeitschriftentitel:
Nat Genet
Jahr:
2022
Band / Volume:
54
Heft / Issue:
5
Seitenangaben Beitrag:
560-572
Volltext / DOI:
doi:10.1038/s41588-022-01058-3
PubMed:
http://view.ncbi.nlm.nih.gov/pubmed/35551307
Print-ISSN:
1061-4036
TUM Einrichtung:
656; Institut für Humangenetik
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