A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure

Research output: Contribution to journalArticle

Authors

  • The CHARGE Neurology Working Group
  • The COGENT-Kidney Consortium
  • The GIANT consortium
  • Lifelines Cohort Study

External Institution(s)

  • Washington University St. Louis
  • University of Regensburg
  • National Institutes of Health
  • University of Texas Health Science Center at Houston
  • Queen Mary University of London
  • University of California at Los Angeles
  • University of North Carolina at Chapel Hill
  • Icahn School of Medicine at Mount Sinai
  • Singapore National Eye Center
  • National University of Singapore
  • National University Health System
  • Erasmus University Rotterdam
  • University of Edinburgh
  • University of Mississippi
  • University of Georgia
  • University of Copenhagen
  • Leiden University
  • Harvard University
  • Institut Pasteur Paris
  • University of Washington
  • Agency for Science, Technology and Research
  • Wake Forest University
  • Broad Institute
  • LSU Pennington Biomedical Research Center
  • Icelandic Heart Association
  • University of Iceland
  • Loyola University Chicago
  • University of Michigan, Ann Arbor
  • Boston University
  • RIKEN
  • University of Tartu
  • University of Groningen
  • University of Lille
  • Karolinska Institutet
  • University of Trieste
  • Tampere University
  • Tampere University Hospital
  • University of Kelaniya
  • Helmholtz Zentrum München - German Research Center for Environmental Health
  • Tunghai University
  • Veterans General Hospital-Taichung Taiwan
  • University of Cambridge
  • The University of the West Indies
  • Huazhong University of Science and Technology
  • University of Leicester
  • Glenfield Hospital
  • University of Eastern Finland
  • Columbia University
  • National Yang-Ming University
  • National Defense Medical Center Taiwan
  • National Chung Hsing University
  • International Medical Center of Japan
  • Lund University
  • Case Western Reserve University
  • University of Greifswald
  • German Centre for Cardiovascular Research
  • Vanderbilt University
  • Johns Hopkins University
  • Imperial College London
  • Ealing Hospital
  • Medical College of Wisconsin
  • Indian Institute of Science Bangalore
  • University of Southern Denmark
  • University of Dundee School of Medicine
  • Université de Bordeaux
  • University Hospital
  • Brown University
  • University of Geneva
  • University of Ioannina
  • Hadassah University Medical Centre
  • Chinese Academy of Medical Sciences
  • Tulane University
  • University of Tokyo
  • Union Memorial Hospital
  • Georgetown/Howard Universities Center for Clinical and Translational Research
  • University of Utah
  • Weill Cornell Medical College in Qatar
  • University of Alabama at Birmingham
  • Osaka University Graduate School of Medicine
  • National Institute for Health and Welfare
  • University of Helsinki
  • Instituto do Coração do Hospital das Clínicas
  • Fred Hutchinson Cancer Research Center
  • Northwestern University
  • University of Oxford
  • Technical University of Munich
  • University of Liverpool
  • University of Aberdeen
  • Data Tecnica InternationalGlen Echo
  • Colorado State University
  • University of Ibadan
  • University of Glasgow
  • University of Minnesota Twin Cities
  • University of Split
  • University of Turku
  • Umeå University
  • IRCCS Burlo
  • University of Iowa
  • University of Edinburgh Medical School
  • Ludwig Maximilian University of Munich
  • Stanford University
  • Capital Medical University
  • Jackson State University
  • University of Pittsburgh
  • Massachusetts Institute of Technology
  • Division Experimental Genetics
  • German Center for Diabetes Research (DZD e.V.)
  • Universidade Federal de Pelotas
  • Heidelberg University 
  • Fimlab Laboratories
  • China Medical University Taichung
  • University of Maryland, Baltimore
  • Kaiser Permanente
  • University of Kentucky
  • University of Southern California

Details

Original languageEnglish (US)
Pages (from-to)375-400
Number of pages26
JournalAmerican journal of human genetics
Volume102
Issue number3
StatusPublished - Mar 1 2018
Peer-reviewedYes

Abstract

Genome-wide association analysis advanced understanding of blood pressure (BP), a major risk factor for vascular conditions such as coronary heart disease and stroke. Accounting for smoking behavior may help identify BP loci and extend our knowledge of its genetic architecture. We performed genome-wide association meta-analyses of systolic and diastolic BP incorporating gene-smoking interactions in 610,091 individuals. Stage 1 analysis examined ∼18.8 million SNPs and small insertion/deletion variants in 129,913 individuals from four ancestries (European, African, Asian, and Hispanic) with follow-up analysis of promising variants in 480,178 additional individuals from five ancestries. We identified 15 loci that were genome-wide significant (p < 5 × 10−8) in stage 1 and formally replicated in stage 2. A combined stage 1 and 2 meta-analysis identified 66 additional genome-wide significant loci (13, 35, and 18 loci in European, African, and trans-ancestry, respectively). A total of 56 known BP loci were also identified by our results (p < 5 × 10−8). Of the newly identified loci, ten showed significant interaction with smoking status, but none of them were replicated in stage 2. Several loci were identified in African ancestry, highlighting the importance of genetic studies in diverse populations. The identified loci show strong evidence for regulatory features and support shared pathophysiology with cardiometabolic and addiction traits. They also highlight a role in BP regulation for biological candidates such as modulators of vascular structure and function (CDKN1B, BCAR1-CFDP1, PXDN, EEA1), ciliopathies (SDCCAG8, RPGRIP1L), telomere maintenance (TNKS, PINX1, AKTIP), and central dopaminergic signaling (MSRA, EBF2).

    Research areas

  • GWAS, GxE interactions, blood pressure, lifestyle, multi-ancestry, smoking

Citation formats

APA

The CHARGE Neurology Working Group, The COGENT-Kidney Consortium, The GIANT consortium, & Lifelines Cohort Study (2018). A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure. American journal of human genetics, 102(3), 375-400. https://doi.org/10.1016/j.ajhg.2018.01.015

Harvard

The CHARGE Neurology Working Group, The COGENT-Kidney Consortium, The GIANT consortium & Lifelines Cohort Study 2018, 'A Large-Scale Multi-ancestry Genome-wide Study Accounting for Smoking Behavior Identifies Multiple Significant Loci for Blood Pressure', American journal of human genetics, vol. 102, no. 3, pp. 375-400. https://doi.org/10.1016/j.ajhg.2018.01.015