Genetics of blood lipids among ~300,000 multi-ethnic participants of the Million Veteran Program

The Geisinger-Regeneron DiscovEHR Collaboration, The VA Million Veteran Program, Global Lipids Genetics Consortium, Myocardial Infarction Genetics (MIGen) Consortium

Research output: Contribution to journalArticle

90 Scopus citations

Abstract

The Million Veteran Program (MVP) was established in 2011 as a national research initiative to determine how genetic variation influences the health of US military veterans. Here we genotyped 312,571 MVP participants using a custom biobank array and linked the genetic data to laboratory and clinical phenotypes extracted from electronic health records covering a median of 10.0 years of follow-up. Among 297,626 veterans with at least one blood lipid measurement, including 57,332 black and 24,743 Hispanic participants, we tested up to around 32 million variants for association with lipid levels and identified 118 novel genome-wide significant loci after meta-analysis with data from the Global Lipids Genetics Consortium (total n > 600,000). Through a focus on mutations predicted to result in a loss of gene function and a phenome-wide association study, we propose novel indications for pharmaceutical inhibitors targeting PCSK9 (abdominal aortic aneurysm), ANGPTL4 (type 2 diabetes) and PDE3B (triglycerides and coronary disease).

Original languageEnglish (US)
Pages (from-to)1514-1523
Number of pages10
JournalNature Genetics
Volume50
Issue number11
DOIs
StatePublished - Nov 1 2018

All Science Journal Classification (ASJC) codes

  • Genetics

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    The Geisinger-Regeneron DiscovEHR Collaboration, The VA Million Veteran Program, Global Lipids Genetics Consortium, & Myocardial Infarction Genetics (MIGen) Consortium (2018). Genetics of blood lipids among ~300,000 multi-ethnic participants of the Million Veteran Program. Nature Genetics, 50(11), 1514-1523. https://doi.org/10.1038/s41588-018-0222-9