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

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).

• Authors: Derek Klarin, Scott M Damrauer, Kelly Cho, Yan V Sun, Tanya M Teslovich, Jacqueline Honerlaw, David R Gagnon, Scott L DuVall, Jin Li, Gina M Peloso, Mark Chaffin, Aeron M Small, Jie Huang, Hua Tang, Julie A Lynch, Yuk-Lam Ho, Dajiang J Liu, Connor A Emdin, Alexander H Li, Jennifer E Huffman, Jennifer S Lee, Pradeep Natarajan, Rajiv Chowdhury, Danish Saleheen, Marijana Vujkovic, Aris Baras, Saiju Pyarajan, Emanuele Di Angelantonio, Benjamin M Neale, Aliya Naheed, Amit V Khera, John Danesh, Kyong-Mi Chang, Gonçalo Abecasis, Cristen Willer, Frederick E Dewey, David J Carey, Global Lipids Genetics Consortium, Myocardial Infarction Genetics (MIGen) Consortium, Geisinger-Regeneron DiscovEHR Collaboration, VA Million Veteran Program, John Concato, J Michael Gaziano, Christopher J O'Donnell, Philip S Tsao, Sekar Kathiresan, Daniel J Rader, Peter W F Wilson, Themistocles L Assimes
• Journal: Nature genetics (Nat Genet) Vol. 50 Issue 11 Pg. 1514-1523 (11 2018) ISSN: 1546-1718 [Electronic] United States
• PMID: 30275531 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Lipids

Topics

• Aged
• Black People (genetics, statistics & numerical data)
• Cardiovascular Diseases (blood, ethnology, genetics)
• Diabetes Mellitus, Type 2 (blood, ethnology, genetics)
• Ethnicity (genetics, statistics & numerical data)
• Female
• Genome-Wide Association Study
• Genotype
• Hispanic or Latino (genetics, statistics & numerical data)
• Humans
• Lipid Metabolism (genetics)
• Lipids (blood)
• Male
• Middle Aged
• Polymorphism, Single Nucleotide
• Veterans (statistics & numerical data)
• White People (genetics, statistics & numerical data)