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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.

Publication ,  Journal Article
Vujkovic, M; Keaton, JM; Lynch, JA; Miller, DR; Zhou, J; Tcheandjieu, C; Huffman, JE; Assimes, TL; Lorenz, K; Zhu, X; Hilliard, AT; Judy, RL ...
Published in: Nat Genet
July 2020

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.

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Published In

Nat Genet

DOI

EISSN

1546-1718

Publication Date

July 2020

Volume

52

Issue

7

Start / End Page

680 / 691

Location

United States

Related Subject Headings

  • Risk Assessment
  • Polymorphism, Single Nucleotide
  • Male
  • Hypoglycemic Agents
  • Humans
  • Genetic Predisposition to Disease
  • Genetic Association Studies
  • Female
  • Europe
  • Diabetic Angiopathies
 

Citation

APA
Chicago
ICMJE
MLA
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Vujkovic, M., Keaton, J. M., Lynch, J. A., Miller, D. R., Zhou, J., Tcheandjieu, C., … Saleheen, D. (2020). 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. Nat Genet, 52(7), 680–691. https://doi.org/10.1038/s41588-020-0637-y
Vujkovic, Marijana, Jacob M. Keaton, Julie A. Lynch, Donald R. Miller, Jin Zhou, Catherine Tcheandjieu, Jennifer E. Huffman, et al. “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.Nat Genet 52, no. 7 (July 2020): 680–91. https://doi.org/10.1038/s41588-020-0637-y.
Vujkovic M, Keaton JM, Lynch JA, Miller DR, Zhou J, Tcheandjieu C, et al. 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. Nat Genet. 2020 Jul;52(7):680–91.
Vujkovic, Marijana, et al. “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.Nat Genet, vol. 52, no. 7, July 2020, pp. 680–91. Pubmed, doi:10.1038/s41588-020-0637-y.
Vujkovic M, Keaton JM, Lynch JA, Miller DR, Zhou J, Tcheandjieu C, Huffman JE, Assimes TL, Lorenz K, Zhu X, Hilliard AT, Judy RL, Huang J, Lee KM, Klarin D, Pyarajan S, Danesh J, Melander O, Rasheed A, Mallick NH, Hameed S, Qureshi IH, Afzal MN, Malik U, Jalal A, Abbas S, Sheng X, Gao L, Kaestner KH, Susztak K, Sun YV, DuVall SL, Cho K, Lee JS, Gaziano JM, Phillips LS, Meigs JB, Reaven PD, Wilson PW, Edwards TL, Rader DJ, Damrauer SM, O’Donnell CJ, Tsao PS, HPAP Consortium, Regeneron Genetics Center, VA Million Veteran Program, Chang K-M, Voight BF, Saleheen D. 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. Nat Genet. 2020 Jul;52(7):680–691.

Published In

Nat Genet

DOI

EISSN

1546-1718

Publication Date

July 2020

Volume

52

Issue

7

Start / End Page

680 / 691

Location

United States

Related Subject Headings

  • Risk Assessment
  • Polymorphism, Single Nucleotide
  • Male
  • Hypoglycemic Agents
  • Humans
  • Genetic Predisposition to Disease
  • Genetic Association Studies
  • Female
  • Europe
  • Diabetic Angiopathies