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

21 Citations (Scopus)

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

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Veterans
Lipids
Electronic Health Records
Abdominal Aortic Aneurysm
Hispanic Americans
Type 2 Diabetes Mellitus
Coronary Disease
Meta-Analysis
Triglycerides
Genome
Phenotype
Mutation
Health
Research
Pharmaceutical Preparations
Genes

All Science Journal Classification (ASJC) codes

  • Genetics

Cite this

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
The Geisinger-Regeneron DiscovEHR Collaboration ; The VA Million Veteran Program ; Global Lipids Genetics Consortium ; Myocardial Infarction Genetics (MIGen) Consortium. / Genetics of blood lipids among ~300,000 multi-ethnic participants of the Million Veteran Program. In: Nature Genetics. 2018 ; Vol. 50, No. 11. pp. 1514-1523.
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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, vol. 50, no. 11, pp. 1514-1523. https://doi.org/10.1038/s41588-018-0222-9

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.

In: Nature Genetics, Vol. 50, No. 11, 01.11.2018, p. 1514-1523.

Research output: Contribution to journalArticle

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AU - Myocardial Infarction Genetics (MIGen) Consortium

AU - Klarin, Derek

AU - Damrauer, Scott M.

AU - Cho, Kelly

AU - Sun, Yan V.

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AU - Gagnon, David R.

AU - DuVall, Scott L.

AU - Li, Jin

AU - Peloso, Gina M.

AU - Chaffin, Mark

AU - Small, Aeron M.

AU - Huang, Jie

AU - Tang, Hua

AU - Lynch, Julie A.

AU - Ho, Yuk Lam

AU - Liu, Dajiang

AU - Emdin, Connor A.

AU - Li, Alexander H.

AU - Huffman, Jennifer E.

AU - Lee, Jennifer S.

AU - Natarajan, Pradeep

AU - Chowdhury, Rajiv

AU - Saleheen, Danish

AU - Vujkovic, Marijana

AU - Baras, Aris

AU - Pyarajan, Saiju

AU - Di Angelantonio, Emanuele

AU - Neale, Benjamin M.

AU - Naheed, Aliya

AU - Khera, Amit V.

AU - Danesh, John

AU - Chang, Kyong Mi

AU - Abecasis, Gonçalo

AU - Willer, Cristen

AU - Dewey, Frederick E.

AU - Carey, David J.

AU - Concato, John

AU - Gaziano, J. Michael

AU - O’Donnell, Christopher J.

AU - Tsao, Philip S.

AU - Kathiresan, Sekar

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The Geisinger-Regeneron DiscovEHR Collaboration, The VA Million Veteran Program, Global Lipids Genetics Consortium, Myocardial Infarction Genetics (MIGen) Consortium. Genetics of blood lipids among ~300,000 multi-ethnic participants of the Million Veteran Program. Nature Genetics. 2018 Nov 1;50(11):1514-1523. https://doi.org/10.1038/s41588-018-0222-9