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Olle Melander

Principal investigator

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Discovery of 318 new risk loci for type 2 diabetes and related vascular outcomes among 1.4 million participants in a multi-ancestry meta-analysis

Author

  • Marijana Vujkovic
  • Olle Melander
  • Danish Saleheen

Summary, in English

We investigated type 2 diabetes (T2D) genetic susceptibility via multi-ancestry meta-analysis of 228,499 cases and 1,178,783 controls in the Million Veteran Program (MVP), DIAMANTE, Biobank Japan and other studies. We report 568 associations, including 286 autosomal, 7 X-chromosomal and 25 identified in ancestry-specific analyses that were previously unreported. Transcriptome-wide association analysis detected 3,568 T2D associations with genetically predicted gene expression in 687 novel genes; of these, 54 are known to interact with FDA-approved drugs. A polygenic risk score (PRS) was strongly associated with increased risk of T2D-related retinopathy and modestly associated with chronic kidney disease (CKD), peripheral artery disease (PAD) and neuropathy. We investigated the genetic etiology of T2D-related vascular outcomes in the MVP and observed statistical SNP–T2D interactions at 13 variants, including coronary heart disease (CHD), CKD, PAD and neuropathy. These findings may help to identify potential therapeutic targets for T2D and genomic pathways that link T2D to vascular outcomes. © 2020, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.

Department/s

  • EXODIAB: Excellence in Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health
  • Cardiovascular Research - Hypertension

Publishing year

2020

Language

English

Pages

680-691

Publication/Series

Nature Genetics

Volume

52

Issue

7

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Medical Genetics
  • Endocrinology and Diabetes

Status

Published

Research group

  • Cardiovascular Research - Hypertension

ISBN/ISSN/Other

  • ISSN: 1546-1718