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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-10-01

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, , , , , John Concato, J. Michael Gaziano, Christopher J. O’Donnell, Philip S. Tsao, Sekar Kathiresan, Daniel J. Rader, Peter W. F. Wilson, Themistocles L. Assimes

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). More... »

PAGES

1514-1523

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  • Journal

    TITLE

    Nature Genetics

    ISSUE

    11

    VOLUME

    50

    Author Affiliations

  • Boston VA Healthcare System, Boston, MA, USA
  • Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
  • Massachusetts Veterans Epidemiology Research and Information Center (MAVERIC), VA Boston Healthcare System, Boston, MA, USA
  • Department of Epidemiology, Rollins School of Public Health, Department of Biomedical Informatics, School of Medicine, Emory University, Atlanta, GA, USA
  • Regeneron Genetics Center, Tarrytown, NY, USA
  • Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA
  • Department of Medicine, University of Utah School of Medicine, Salt Lake City, UT, USA
  • VA Palo Alto Health Care System, Palo Alto, CA, USA
  • Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Department of Medicine, Yale School of Medicine, New Haven, CT, USA
  • Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA
  • University of Massachusetts College of Nursing and Health Sciences, Boston, MA, USA
  • Department of Public Health Sciences, Institute of Personalized Medicine, Penn State College of Medicine, Hershey, PA, USA
  • Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
  • Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
  • Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
  • Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
  • Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Initiative for Noncommunicable Diseases, Health Systems and Population Studies Division, International Centre for Diarrheal Disease Research, Dhaka, Bangladesh
  • Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
  • Center for Statistical Genetics, Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA
  • Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA
  • Geisinger Health System, Danville, PA, USA
  • Clinical Epidemiology Research Center, VA Connecticut Healthcare System, West Haven, CT, USA
  • Department of Medicine, Harvard Medical School, Boston, MA, USA
  • Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
  • Emory Clinical Cardiovascular Research Institute, Atlanta, GA, USA
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41588-018-0222-9

    DOI

    http://dx.doi.org/10.1038/s41588-018-0222-9

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1107327384

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30275531


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