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Klarin, D.* ; Damrauer, S.M.* ; Cho, K.-H.* ; Sun, Y.* ; Teslovich, T.M.* ; Honerlaw, J.* ; Gagnon, D.R.* ; Du Vall, S.L.* ; Li, J.* ; Peloso, G.M.* ; Chaffin, M.* ; Small, A.M.* ; Huang, J.* ; Tang, H.* ; Lynch, J.A.* ; Ho, Y.H.* ; Liu, D.* ; Emdin, C.A.* ; Li, A.H.* ; Huffman, J.E.* ; Lee, J.S.* ; Natarajan, P.* ; Chowdhury, R.* ; Saleheen, D.* ; Vujkovic, M.R.* ; Baras, A.* ; Pyarajan, S.* ; di Angelantonio, E.* ; Neale, B.M.* ; Naheed, A.I.* ; Khera, A.V.* ; Danesh, J.* ; Chan, K.* ; Abecasis, G.* ; Willer, C.* ; Dewey, F.E.* ; Carey, D.J.* ; Concato, J.* ; Gaziano, J.M.* ; O'Donnell, C.* ; Tsao, P.S.* ; Kathiresan, S.* ; Rader, D.J.* ; Wilson, P.W.F.* ; Assimes, T.L.* ; Global Lipids Genetics Consortium (Strauch, K. ; Gieger, C. ; Grallert, H. ; Müller-Nurasyid, M. ; Peters, A. ; Waldenberger, M.)

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

Nat. Genet. 50, 1514-1523 (2018)
Postprint DOI PMC
Open Access Green
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).
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Coronary-artery-disease; Genome-wide Association; Coding Variants; Heart-disease; Low-frequency; Loci; Risk; Metaanalysis; Mutations; Biobank
ISSN (print) / ISBN 1061-4036
e-ISSN 1546-1718
Journal Nature Genetics
Quellenangaben Volume: 50, Issue: 11, Pages: 1514-1523 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place New York, NY
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Genetic Epidemiology (IGE)
Institute of Epidemiology II (EPI2)