Multi-ethnic genome-wide association study for atrial fibrillation View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-06-11

AUTHORS

Carolina Roselli, Mark D. Chaffin, Lu-Chen Weng, Stefanie Aeschbacher, Gustav Ahlberg, Christine M. Albert, Peter Almgren, Alvaro Alonso, Christopher D. Anderson, Krishna G. Aragam, Dan E. Arking, John Barnard, Traci M. Bartz, Emelia J. Benjamin, Nathan A. Bihlmeyer, Joshua C. Bis, Heather L. Bloom, Eric Boerwinkle, Erwin B. Bottinger, Jennifer A. Brody, Hugh Calkins, Archie Campbell, Thomas P. Cappola, John Carlquist, Daniel I. Chasman, Lin Y. Chen, Yii-Der Ida Chen, Eue-Keun Choi, Seung Hoan Choi, Ingrid E. Christophersen, Mina K. Chung, John W. Cole, David Conen, James Cook, Harry J. Crijns, Michael J. Cutler, Scott M. Damrauer, Brian R. Daniels, Dawood Darbar, Graciela Delgado, Joshua C. Denny, Martin Dichgans, Marcus Dörr, Elton A. Dudink, Samuel C. Dudley, Nada Esa, Tonu Esko, Markku Eskola, Diane Fatkin, Stephan B. Felix, Ian Ford, Oscar H. Franco, Bastiaan Geelhoed, Raji P. Grewal, Vilmundur Gudnason, Xiuqing Guo, Namrata Gupta, Stefan Gustafsson, Rebecca Gutmann, Anders Hamsten, Tamara B. Harris, Caroline Hayward, Susan R. Heckbert, Jussi Hernesniemi, Lynne J. Hocking, Albert Hofman, Andrea R. V. R. Horimoto, Jie Huang, Paul L. Huang, Jennifer Huffman, Erik Ingelsson, Esra Gucuk Ipek, Kaoru Ito, Jordi Jimenez-Conde, Renee Johnson, J. Wouter Jukema, Stefan Kääb, Mika Kähönen, Yoichiro Kamatani, John P. Kane, Adnan Kastrati, Sekar Kathiresan, Petra Katschnig-Winter, Maryam Kavousi, Thorsten Kessler, Bas L. Kietselaer, Paulus Kirchhof, Marcus E. Kleber, Stacey Knight, Jose E. Krieger, Michiaki Kubo, Lenore J. Launer, Jari Laurikka, Terho Lehtimäki, Kirsten Leineweber, Rozenn N. Lemaitre, Man Li, Hong Euy Lim, Henry J. Lin, Honghuang Lin, Lars Lind, Cecilia M. Lindgren, Marja-Liisa Lokki, Barry London, Ruth J. F. Loos, Siew-Kee Low, Yingchang Lu, Leo-Pekka Lyytikäinen, Peter W. Macfarlane, Patrik K. Magnusson, Anubha Mahajan, Rainer Malik, Alfredo J. Mansur, Gregory M. Marcus, Lauren Margolin, Kenneth B. Margulies, Winfried März, David D. McManus, Olle Melander, Sanghamitra Mohanty, Jay A. Montgomery, Michael P. Morley, Andrew P. Morris, Martina Müller-Nurasyid, Andrea Natale, Saman Nazarian, Benjamin Neumann, Christopher Newton-Cheh, Maartje N. Niemeijer, Kjell Nikus, Peter Nilsson, Raymond Noordam, Heidi Oellers, Morten S. Olesen, Marju Orho-Melander, Sandosh Padmanabhan, Hui-Nam Pak, Guillaume Paré, Nancy L. Pedersen, Joanna Pera, Alexandre Pereira, David Porteous, Bruce M. Psaty, Sara L. Pulit, Clive R. Pullinger, Daniel J. Rader, Lena Refsgaard, Marta Ribasés, Paul M. Ridker, Michiel Rienstra, Lorenz Risch, Dan M. Roden, Jonathan Rosand, Michael A. Rosenberg, Natalia Rost, Jerome I. Rotter, Samir Saba, Roopinder K. Sandhu, Renate B. Schnabel, Katharina Schramm, Heribert Schunkert, Claudia Schurman, Stuart A. Scott, Ilkka Seppälä, Christian Shaffer, Svati Shah, Alaa A. Shalaby, Jaemin Shim, M. Benjamin Shoemaker, Joylene E. Siland, Juha Sinisalo, Moritz F. Sinner, Agnieszka Slowik, Albert V. Smith, Blair H. Smith, J. Gustav Smith, Jonathan D. Smith, Nicholas L. Smith, Elsayed Z. Soliman, Nona Sotoodehnia, Bruno H. Stricker, Albert Sun, Han Sun, Jesper H. Svendsen, Toshihiro Tanaka, Kahraman Tanriverdi, Kent D. Taylor, Maris Teder-Laving, Alexander Teumer, Sébastien Thériault, Stella Trompet, Nathan R. Tucker, Arnljot Tveit, Andre G. Uitterlinden, Pim Van Der Harst, Isabelle C. Van Gelder, David R. Van Wagoner, Niek Verweij, Efthymia Vlachopoulou, Uwe Völker, Biqi Wang, Peter E. Weeke, Bob Weijs, Raul Weiss, Stefan Weiss, Quinn S. Wells, Kerri L. Wiggins, Jorge A. Wong, Daniel Woo, Bradford B. Worrall, Pil-Sung Yang, Jie Yao, Zachary T. Yoneda, Tanja Zeller, Lingyao Zeng, Steven A. Lubitz, Kathryn L. Lunetta, Patrick T. Ellinor

ABSTRACT

Atrial fibrillation (AF) affects more than 33 million individuals worldwide1 and has a complex heritability2. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF. More... »

PAGES

1225-1233

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  • Journal

    TITLE

    Nature Genetics

    ISSUE

    9

    VOLUME

    50

    Author Affiliations

  • Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA
  • Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA
  • Cardiovascular Research Institute Basel, Basel, Switzerland
  • Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
  • Divisions of Preventive and Cardiovascular Medicine, Brigham and Women’s Hospital & Harvard Medical School, Boston, MA, USA
  • Department of Clinical Sciences, Lund University, Malmo, Sweden
  • Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA
  • Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA
  • McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
  • Departments of Cardiovascular Medicine, Cellular and Molecular Medicine, Molecular Cardiology, and Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA
  • Cardiovascular Health Research Unit, Departments of Medicine and Biostatistics, University of Washington, Seattle, WA, USA
  • Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA
  • Predoctoral Training Program in Human Genetics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
  • Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA
  • Division of Cardiology, Emory University and Atlanta VA Medical Center, Atlanta, GA, USA
  • Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA
  • Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY, USA
  • Johns Hopkins University, Baltimore, MD, USA
  • Generation Scotland, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
  • Penn Cardiovascular Institute and Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
  • Division of Cardiovascular Medicine, University of Utah, Salt Lake City, UT, USA
  • Divisions of Preventive Medicine and Genetics, Brigham and Women’s Hospital & Harvard Medical School, Boston, MA, USA
  • Cardiovascular Division, Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA
  • Institute for Translational Genomics and Population Sciences, Department of Pediatrics, LABioMed at Harbor-UCLA Medical Center, Torrance, CA, USA
  • Seoul National University Hospital, Seoul, Korea
  • Department of Medical Research, Bærum Hospital, Vestre Viken Hospital Trust, Drammen, Norway
  • University of Maryland School of Medicine, Department of Neurology, Baltimore, MD, USA
  • Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada
  • Department of Biostatistics, University of Liverpool, Liverpool, UK
  • Maastricht University Medical Center+ and Cardiovascular Research Institute Maastricht, Department of Cardiology, Maastricht, The Netherlands
  • Intermountain Heart Institute, Intermountain Medical Center, Murray, UT, USA
  • Department of Surgery, Corporal Michael Crescenz VA Medical Center, Philadelphia, PA, USA
  • University of Illinois Chicago, Chicago, IL, USA
  • Vth Department of Medicine, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany
  • Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
  • German Center for Neurodegenerative Diseases (DZNE), Munich, Germany
  • DZHK (German Centre for Cardiovascular Research), partner site: Greifswald, Greifswald, Germany
  • Cardiovascular Division and Lillehei Heart Institute, University of Minnesota, Minneapolis, MN, USA
  • University of Massachusetts Medical School Worcester, Worcester, MA, USA
  • Estonian Genome Center, University of Tartu, Tartu, Estonia
  • Heart Center, Department of Cardiology, Tampere University Hospital, Finland and Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
  • Faculty of Medicine, University of New South Wales, Kensington, New South Wales, Australia
  • Robertson Center for Biostatistics, University of Glasgow, Glasgow, UK
  • Department of Epidemiology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands
  • Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
  • School of Health and Medical Sciences, Seton Hall University, South Orange, NJ, USA
  • Faculty of Medicine, University of Iceland, Reykavik, Iceland
  • Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden
  • Division of Cardiovascular Medicine and Abboud Cardiovascular Research Center, University of Iowa, Iowa City, IA, USA
  • Cardiovascular Genetics and Genomics Group, Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
  • Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, Bethesda, MD, USA
  • MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
  • Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA
  • Department of Clinical Chemistry, Fimlab Laboratories and Finnish Cardiovascular Research Center–Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
  • Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK
  • Laboratory of Genetics and Molecular Cardiology, Heart Institute, University of São Paulo, São Paulo, Brazil
  • Boston VA Research Institute, Inc., Boston, MA, USA
  • Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
  • Laboratory for Cardiovascular Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
  • Universitat Autònoma de Barcelona, Medicine Department, Barcelona, Spain
  • Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia
  • Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands
  • DZHK (German Centre for Cardiovascular Research), partner site: Munich Heart Alliance, Munich, Germany
  • Department of Clinical Physiology, Tampere University Hospital, and Finnish Cardiovascular Research Center–Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
  • Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
  • Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA, USA
  • Deutsches Herzzentrum München, Klinik für Herz- und Kreislauferkrankungen, Technische Universität München, Munich, Germany
  • Department of Neurology, Medical University of Graz, Graz, Austria
  • AFNET, Muenster, Germany
  • Department of Medicine, University of Utah, Salt Lake City, UT, USA
  • RIKEN Center for Integrative Medical Sciences, Yokohama, Japan
  • Department of Cardio-Thoracic Surgery, Heart Center, Tampere University Hospital, and Finnish Cardiovascular Research Center–Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
  • Dept. Disease Genomics, Bayer, Wuppertal, Germany
  • Division of Nephrology & Hypertension, Internal Medicine, School of Medicine, University of Utah, Salt Lake City, UT, USA
  • Korea University Guro Hospital, Seoul, Korea
  • Department of Medicine, Boston University School of Medicine, Boston, MA, USA
  • Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden
  • Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
  • Transplantation Laboratory, Medicum, University of Helsinki, Helsinki, Finland
  • The Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
  • The Genetics of Obesity and Related Metabolic Traits Program, Icahn School of Medicine at Mount Sinai, New York, New York, USA
  • Institute of Health and Wellbeing, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
  • Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
  • Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany
  • Heart Institute, University of São Paulo, São Paulo, Brazil
  • Division of Cardiology, University of California, San Francisco, San Francisco, California, USA
  • Synlab Academy, Synlab Services GmbH, Mannheim, Germany
  • Department of Internal Medicine, Clinical Sciences, Lund University, Malmo, Sweden
  • Dell Medical School, Austin, TX, USA
  • Institute of Genetic Epidemiology, Helmholtz Zentrum München–German Research Center for Environmental Health, Neuherberg, Germany
  • University of Pennsylvania, Philadelphia, PA, USA
  • Department of Medicine I, University Hospital Munich, Ludwig-Maximilians-University, Munich, Germany
  • Department of Clinical Sciences, Lund University and Skåne University Hospital, Malmo, Sweden
  • Section of Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands
  • Atrial Fibrillation NETwork, Muenster, Germany
  • Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK
  • Yonsei University Health System, Seoul, Korea
  • Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada
  • Department of Neurology, Faculty of Medicine, Jagiellonian University Medical College, Krakow, Poland
  • Department of Genetics, Harvard Medical School, Boston, MA, USA
  • Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, WA, USA
  • Li Ka Shing Center for Health Information and Discovery, Big Data Institute, Oxford University, Oxford, UK
  • Division of Cardiovascular Medicine, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
  • Biomedical Network Research Centre on Mental Health (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain
  • Labormedizinisches Zentrum Dr. Risch, Schaan, Liechtenstein
  • University of Colorado School of Medicine, Aurora, CO, USA
  • J. Philip Kistler Stroke Research Center, Massachusetts General Hospital, Boston, MA, USA
  • Institute for Translational Genomics and Population Sciences, Departments of Pediatrics and Medicine, LABioMed at Harbor-UCLA Medical Center, Torrance, CA, USA
  • Division of Cardiology, University of Pittsburgh, Pittsburgh, PA, USA
  • Division of Cardiology, University of Alberta, Edmonton, Alberta, Canada
  • DZHK (German Centre for Cardiovascular Research), partner site: Hamburg/Kiel/Lübeck, Hamburg, Germany
  • Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA
  • Division of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA
  • Cardiology Division, Pittsburgh VA Healthcare System, Pittsburgh, Pennsylvania, USA
  • Korea University Anam Hospital, Seoul, Korea
  • Heart and Lung Center HUS, Helsinki University Central Hospital, Helsinki, Finland
  • Division of Population Health Sciences, University of Dundee, Dundee, UK
  • Department of Cardiology, Clinical Sciences, Lund University and Skåne University Hospital, Lund, Sweden
  • Epidemiological Cardiology Research Center (EPICARE), Wake Forest School of Medicine, Winston Salem, NC, USA
  • Cardiovascular Health Research Unit, Departments of Medicine and Epidemiology, University of Washington, Seattle, WA, USA
  • Inspectorate of Health Care, Utrecht, The Netherlands
  • Department of Human Genetics and Disease Diversity, Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences, Tokyo, Japan
  • Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany
  • Institute of Clinical Medicine, University of Oslo, Oslo, Norway
  • Department of Epidemiology and Internal Medicine, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands
  • Interfaculty Institute for Genetics and Functional Genomics, University Medicine and Ernst-Moritz-Arndt-University Greifswald, Greifswald, Germany
  • Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA
  • Division of Cardiovascular Medicine, The Ohio State University, Columbus, OH, USA
  • Division of Cardiology, Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada
  • University of Cincinnati College of Medicine, Cincinnati, OH, USA
  • Departments of Neurology and Public Health Science, University of Virginia Health System, Charlottesville, VA, USA
  • Cardiac Arrhythmia Service, Massachusetts General Hospital, Boston, MA, USA
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/s41588-018-0133-9

    DOI

    http://dx.doi.org/10.1038/s41588-018-0133-9

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1104478460

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/29892015


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