@article{e6dfa68fd0ea4a2286b03c39eaea5abd,
title = "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",
abstract = "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.",
author = "{The HPAP Consortium} and {Regeneron Genetics Center} and {VA Million Veteran Program} and Marijana Vujkovic and Keaton, {Jacob M.} and Lynch, {Julie A.} and Miller, {Donald R.} and Jin Zhou and Catherine Tcheandjieu and Huffman, {Jennifer E.} and Assimes, {Themistocles L.} and Kimberly Lorenz and Xiang Zhu and Hilliard, {Austin T.} and Judy, {Renae L.} and Jie Huang and Lee, {Kyung M.} and Derek Klarin and Saiju Pyarajan and John Danesh and Olle Melander and Asif Rasheed and Mallick, {Nadeem H.} and Shahid Hameed and Qureshi, {Irshad H.} and Afzal, {Muhammad Naeem} and Uzma Malik and Anjum Jalal and Shahid Abbas and Xin Sheng and Long Gao and Kaestner, {Klaus H.} and Katalin Susztak and Sun, {Yan V.} and DuVall, {Scott L.} and Kelly Cho and Lee, {Jennifer S.} and Gaziano, {J. Michael} and Phillips, {Lawrence S.} and Meigs, {James B.} and Reaven, {Peter D.} and Wilson, {Peter W.} and Edwards, {Todd L.} and Rader, {Daniel J.} and Damrauer, {Scott M.} and O{\textquoteright}Donnell, {Christopher J.} and Tsao, {Philip S.} and Atkinson, {Mark A.} and Powers, {Al C.} and Ali Naji and Kaestner, {Klaus H.} and Abecasis, {Goncalo R.} and Ahuja, {Sunil K.}",
note = "Publisher Copyright: {\textcopyright} 2020, This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.",
year = "2020",
month = jul,
day = "1",
doi = "10.1038/s41588-020-0637-y",
language = "English (US)",
volume = "52",
pages = "680--691",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "Nature Publishing Group",
number = "7",
}