Genetics of blood lipids among ~300,000 multi-ethnic participants of the Million Veteran Program.
Authors
Klarin, Derek
Damrauer, Scott M
Cho, Kelly
Sun, Yan V
Teslovich, Tanya M
Honerlaw, Jacqueline
DuVall, Scott L
Li, Jin
Peloso, Gina M
Small, Aeron M
Huang, Jie
Tang, Hua
Lynch, Julie A
Ho, Yuk-Lam
Liu, Dajiang J
Li, Alexander H
Lee, Jennifer S
Natarajan, Pradeep
Chowdhury, Rajiv
Saleheen, Danish
Baras, Aris
Pyarajan, Saiju
Di Angelantonio, Emanuele
Naheed, Aliya
Khera, Amit V
Danesh, John
Chang, Kyong-Mi
Abecasis, Gonçalo
Dewey, Frederick E
Carey, David J
Global Lipids Genetics Consortium
Myocardial Infarction Genetics (MIGen) Consortium
Geisinger-Regeneron DiscovEHR Collaboration
VA Million Veteran Program
Concato, John
Gaziano, J Michael
O'Donnell, Christopher J
Tsao, Philip S
Rader, Daniel J
Wilson, Peter WF
Publication Date
2018-11Journal Title
Nat Genet
ISSN
1061-4036
Publisher
Springer Science and Business Media LLC
Volume
50
Issue
11
Pages
1514-1523
Language
eng
Type
Article
Physical Medium
Print-Electronic
Metadata
Show full item recordCitation
Klarin, D., Damrauer, S. M., Cho, K., Sun, Y. V., Teslovich, T. M., Honerlaw, J., Gagnon, D. R., et al. (2018). Genetics of blood lipids among ~300,000 multi-ethnic participants of the Million Veteran Program.. Nat Genet, 50 (11), 1514-1523. https://doi.org/10.1038/s41588-018-0222-9
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).
Keywords
Aged, Black People, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Ethnicity, Female, Genome-Wide Association Study, Genotype, Hispanic or Latino, Humans, Lipid Metabolism, Lipids, Male, Middle Aged, Polymorphism, Single Nucleotide, Veterans, White People
Sponsorship
Medical Research Council (MR/L003120/1)
British Heart Foundation (None)
Identifiers
External DOI: https://doi.org/10.1038/s41588-018-0222-9
This record's URL: https://www.repository.cam.ac.uk/handle/1810/279839
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http://www.rioxx.net/licenses/all-rights-reserved
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