Genetics of blood lipids among ~300,000 multi-ethnic participants of the Million Veteran Program.
Authors
Klarin, Derek
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
Saleheen, Danish
Baras, Aris
Pyarajan, Saiju
Khera, Amit V
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
Nature genetics
ISSN
1061-4036
Publisher
Springer Nature
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.. Nature genetics, 50 (11), 1514-1523. https://doi.org/10.1038/s41588-018-0222-9
Abstract
The Million Veteran Program was established in 2011 as a national research initiative to determine how genetic variation influences the health of U.S. veterans. We genotyped 312,571 participants of this program 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 1 blood lipid measure including 57,332 blacks and 24,743 Hispanics, we tested up to ~32 million genetic variants for association with blood 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 leading to 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
Global Lipids Genetics Consortium, Myocardial Infarction Genetics (MIGen) Consortium, Geisinger-Regeneron DiscovEHR Collaboration, VA Million Veteran Program, Humans, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Lipids, Genotype, Polymorphism, Single Nucleotide, Aged, Middle Aged, African Continental Ancestry Group, European Continental Ancestry Group, Ethnic Groups, Hispanic Americans, Veterans, Female, Male, Lipid Metabolism, Genome-Wide Association Study
Sponsorship
MRC (MR/L003120/1)
British Heart Foundation (RG/13/13/30194)
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
Rights
Licence:
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