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Multi-ethnic genome-wide association study for atrial fibrillation.
Roselli, Carolina; Chaffin, Mark D; Weng, Lu-Chen; Aeschbacher, Stefanie; Ahlberg, Gustav; Albert, Christine M; Almgren, Peter; Alonso, Alvaro; Anderson, Christopher D; Aragam, Krishna G; Arking, Dan E; Barnard, John; Bartz, Traci M; Benjamin, Emelia J; Bihlmeyer, Nathan A; Bis, Joshua C; Bloom, Heather L; Boerwinkle, Eric; Bottinger, Erwin B; Brody, Jennifer A; Calkins, Hugh; Campbell, Archie; Cappola, Thomas P; Carlquist, John; Chasman, Daniel I; Chen, Lin Y; Chen, Yii-Der Ida; Choi, Eue-Keun; Choi, Seung Hoan; Christophersen, Ingrid E; Chung, Mina K; Cole, John W; Conen, David; Cook, James; Crijns, Harry J; Cutler, Michael J; Damrauer, Scott M; Daniels, Brian R; Darbar, Dawood; Delgado, Graciela; Denny, Joshua C; Dichgans, Martin; Dörr, Marcus; Dudink, Elton A; Dudley, Samuel C; Esa, Nada; Esko, Tonu; Eskola, Markku; Fatkin, Diane; Felix, Stephan B.
Affiliation
  • Roselli C; Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Chaffin MD; Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Weng LC; Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Aeschbacher S; Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.
  • Ahlberg G; University Hospital Basel, Basel, Switzerland.
  • Albert CM; Cardiovascular Research Institute Basel, Basel, Switzerland.
  • Almgren P; Laboratory for Molecular Cardiology, The Heart Centre, Department of Cardiology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
  • Alonso A; The Danish National Research Foundation Centre for Cardiac Arrhythmia, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Anderson CD; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Aragam KG; Divisions of Preventive and Cardiovascular Medicine, Brigham and Women's Hospital & Harvard Medical School, Boston, MA, USA.
  • Arking DE; Department of Clinical Sciences, Lund University, Malmo, Sweden.
  • Barnard J; Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
  • Bartz TM; Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Benjamin EJ; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Bihlmeyer NA; Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Bis JC; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Bloom HL; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Boerwinkle E; Departments of Cardiovascular Medicine, Cellular and Molecular Medicine, Molecular Cardiology, and Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA.
  • Bottinger EB; Cardiovascular Health Research Unit, Departments of Medicine and Biostatistics, University of Washington, Seattle, WA, USA.
  • Brody JA; NHLBI and Boston University's Framingham Heart Study, Framingham, MA, USA.
  • Calkins H; Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
  • Campbell A; Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA.
  • Cappola TP; Predoctoral Training Program in Human Genetics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
  • Carlquist J; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
  • Chasman DI; Division of Cardiology, Emory University and Atlanta VA Medical Center, Atlanta, GA, USA.
  • Chen LY; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
  • Chen YI; The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Choi EK; Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • Choi SH; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
  • Christophersen IE; Johns Hopkins University, Baltimore, MD, USA.
  • Chung MK; Generation Scotland, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
  • Cole JW; Penn Cardiovascular Institute and Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Conen D; Intermountain Heart Institute, Intermountain Medical Center, Murray, UT, USA.
  • Cook J; Division of Cardiovascular Medicine, University of Utah, Salt Lake City, UT, USA.
  • Crijns HJ; Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Cutler MJ; Divisions of Preventive Medicine and Genetics, Brigham and Women's Hospital & Harvard Medical School, Boston, MA, USA.
  • Damrauer SM; Cardiovascular Division, Department of Medicine, University of Minnesota Medical School, Minneapolis, MN, USA.
  • Daniels BR; Institute for Translational Genomics and Population Sciences, Department of Pediatrics, LABioMed at Harbor-UCLA Medical Center, Torrance, CA, USA.
  • Darbar D; Seoul National University Hospital, Seoul, Korea.
  • Delgado G; Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Denny JC; Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Dichgans M; Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.
  • Dörr M; Department of Medical Research, Bærum Hospital, Vestre Viken Hospital Trust, Drammen, Norway.
  • Dudink EA; Departments of Cardiovascular Medicine, Cellular and Molecular Medicine, Molecular Cardiology, and Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA.
  • Dudley SC; Baltimore Veterans Affairs Medical Center, Department of Neurology, Baltimore, MD, USA.
  • Esa N; University of Maryland School of Medicine, Department of Neurology, Baltimore, MD, USA.
  • Esko T; University Hospital Basel, Basel, Switzerland.
  • Eskola M; Cardiovascular Research Institute Basel, Basel, Switzerland.
  • Fatkin D; Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada.
  • Felix SB; Department of Biostatistics, University of Liverpool, Liverpool, UK.
Nat Genet ; 50(9): 1225-1233, 2018 06 11.
Article in En | MEDLINE | ID: mdl-29892015
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Atrial Fibrillation / Ethnicity Type of study: Observational_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limits: Humans Language: En Journal: Nat Genet Journal subject: GENETICA MEDICA Year: 2018 Document type: Article Affiliation country: Estados Unidos
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Atrial Fibrillation / Ethnicity Type of study: Observational_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limits: Humans Language: En Journal: Nat Genet Journal subject: GENETICA MEDICA Year: 2018 Document type: Article Affiliation country: Estados Unidos