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

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).