Rare and low-frequency exonic variants and gene-by-smoking interactions in pulmonary function View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2021-09-29

AUTHORS

Tianzhong Yang, Victoria E. Jackson, Albert V. Smith, Han Chen, Traci M. Bartz, Colleen M. Sitlani, Bruce M. Psaty, Sina A. Gharib, George T. O’Connor, Josée Dupuis, Jiayi Xu, Kurt Lohman, Yongmei Liu, Stephen B. Kritchevsky, Patricia A. Cassano, Claudia Flexeder, Christian Gieger, Stefan Karrasch, Annette Peters, Holger Schulz, Sarah E. Harris, John M. Starr, Ian J. Deary, Ani Manichaikul, Elizabeth C. Oelsner, R. G. Barr, Kent D. Taylor, Stephen S. Rich, Tobias N. Bonten, Dennis O. Mook-Kanamori, Raymond Noordam, Ruifang Li-Gao, Marjo-Riitta Jarvelin, Matthias Wielscher, Natalie Terzikhan, Lies Lahousse, Guy Brusselle, Stefan Weiss, Ralf Ewert, Sven Gläser, Georg Homuth, Nick Shrine, Ian P. Hall, Martin Tobin, Stephanie J. London, Peng Wei, Alanna C. Morrison

ABSTRACT

Genome-wide association studies have identified numerous common genetic variants associated with spirometric measures of pulmonary function, including forced expiratory volume in one second (FEV1), forced vital capacity, and their ratio. However, variants with lower minor allele frequencies are less explored. We conducted a large-scale gene-smoking interaction meta-analysis on exonic rare and low-frequency variants involving 44,429 individuals of European ancestry in the discovery stage and sought replication in the UK BiLEVE study with 45,133 European ancestry samples and UK Biobank study with 59,478 samples. We leveraged data on cigarette smoking, the major environmental risk factor for reduced lung function, by testing gene-by-smoking interaction effects only and simultaneously testing the genetic main effects and interaction effects. The most statistically significant signal that replicated was a previously reported low-frequency signal in GPR126, distinct from common variant associations in this gene. Although only nominal replication was obtained for a top rare variant signal rs142935352 in one of the two studies, interaction and joint tests for current smoking and PDE3B were significantly associated with FEV1. This study investigates the utility of assessing gene-by-smoking interactions and underscores their effects on potential pulmonary function. More... »

PAGES

19365

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  • Journal

    TITLE

    Scientific Reports

    ISSUE

    1

    VOLUME

    11

    Author Affiliations

  • Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, USA
  • Department of Health Sciences, University of Leicester, Leicester, UK
  • Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA
  • Center for Precision Health, School of Public Health and School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, USA
  • Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA
  • Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA
  • Division of Pulmonary, Critical Care, and Sleep, Department of Medicine, University of Washington, Seattle, WA, USA
  • National Heart, Lung, and Blood Institute’s Framingham Heart Study, Framingham, MA, USA
  • Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA
  • Division of Nutritional Sciences, Cornell University, Ithaca, NY, USA
  • Division of Cardiology, Department of Medicine, Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USA
  • Sticht Center for Healthy Aging and Alzheimer’s Prevention, Wake Forest School of Medicine, Winston-Salem, NC, USA
  • Department of Healthcare Policy and Research, Weill Cornell Medical College, New York, NY, USA
  • Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
  • Research Unit of Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
  • Comprehensive Pneumology Center Munich (CPC-M), German Center for Lung Research (DZL), Munich, Germany
  • Institute for Medical Information Processing, Biometry and Epidemiology, Ludwig-Maximilians-Universität München, Munich, Germany
  • Centre for Cognitive Ageing and Cognitive Epidemiology, The University of Edinburgh, Edinburgh, UK
  • Alzheimer Scotland Dementia Research Centre, The University of Edinburgh, Edinburgh, UK
  • Division of Biostatistics and Epidemiology, Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA
  • Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA
  • Department of Medicine, Department of Epidemiology, Columbia University Medical Center, New York, NY, USA
  • David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA
  • Department of Public Health Sciences, Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA
  • Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, The Netherlands
  • Division of Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands
  • Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands
  • Biocenter of Oulu, University of Oulu, Oulu, Finland
  • Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
  • Department of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium
  • DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany
  • Division of Cardiology, Pneumology, Infectious Diseases, Intensive Care Medicine, Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany
  • Department of Internal Medicine, Vivantes Hospital Berlin Spandau, Berlin, Germany
  • Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany
  • Division of Respiratory Medicine, University of Nottingham, Nottingham, UK
  • Leicester Respiratory Biomedical Research Unit, National Institute for Health Research, Glenfield Hospital, Leicester, UK
  • Department of Health and Human Services, Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, USA
  • Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
  • Human Genetics Center, Department of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41598-021-98120-7

    DOI

    http://dx.doi.org/10.1038/s41598-021-98120-7

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1141478290

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/34588469


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