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Biobank-driven genomic discovery yields new insight into atrial fibrillation biology.
Nielsen, Jonas B; Thorolfsdottir, Rosa B; Fritsche, Lars G; Zhou, Wei; Skov, Morten W; Graham, Sarah E; Herron, Todd J; McCarthy, Shane; Schmidt, Ellen M; Sveinbjornsson, Gardar; Surakka, Ida; Mathis, Michael R; Yamazaki, Masatoshi; Crawford, Ryan D; Gabrielsen, Maiken E; Skogholt, Anne Heidi; Holmen, Oddgeir L; Lin, Maoxuan; Wolford, Brooke N; Dey, Rounak; Dalen, Håvard; Sulem, Patrick; Chung, Jonathan H; Backman, Joshua D; Arnar, David O; Thorsteinsdottir, Unnur; Baras, Aris; O'Dushlaine, Colm; Holst, Anders G; Wen, Xiaoquan; Hornsby, Whitney; Dewey, Frederick E; Boehnke, Michael; Kheterpal, Sachin; Mukherjee, Bhramar; Lee, Seunggeun; Kang, Hyun M; Holm, Hilma; Kitzman, Jacob; Shavit, Jordan A; Jalife, José; Brummett, Chad M; Teslovich, Tanya M; Carey, David J; Gudbjartsson, Daniel F; Stefansson, Kari; Abecasis, Gonçalo R; Hveem, Kristian; Willer, Cristen J.
Afiliación
  • Nielsen JB; Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI, USA.
  • Thorolfsdottir RB; Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA.
  • Fritsche LG; deCODE genetics/Amgen, Inc., Reykjavik, Iceland.
  • Zhou W; Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
  • Skov MW; Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI, USA.
  • Graham SE; HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway.
  • Herron TJ; K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health, Norwegian University of Science and Technology, Trondheim, Norway.
  • McCarthy S; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
  • Schmidt EM; Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI, USA.
  • Sveinbjornsson G; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
  • Surakka I; Laboratory of Molecular Cardiology, Department of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
  • Mathis MR; Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI, USA.
  • Yamazaki M; Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA.
  • Crawford RD; Department of Internal Medicine, Center for Arrhythmia Research, University of Michigan, Ann Arbor, MI, USA.
  • Gabrielsen ME; Regeneron Genetics Center, Tarrytown, NY, USA.
  • Skogholt AH; Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.
  • Holmen OL; deCODE genetics/Amgen, Inc., Reykjavik, Iceland.
  • Lin M; Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI, USA.
  • Wolford BN; Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA.
  • Dey R; Department of Anesthesiology, University of Michigan, Ann Arbor, MI, USA.
  • Dalen H; Medical Device Development and Regulation Research Center, The University of Tokyo, Tokyo, Japan.
  • Sulem P; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
  • Chung JH; HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway.
  • Backman JD; K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health, Norwegian University of Science and Technology, Trondheim, Norway.
  • Arnar DO; HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway.
  • Thorsteinsdottir U; K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health, Norwegian University of Science and Technology, Trondheim, Norway.
  • Baras A; HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway.
  • O'Dushlaine C; K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health, Norwegian University of Science and Technology, Trondheim, Norway.
  • Holst AG; Department of Cardiology, St. Olav's University Hospital, Trondheim, Norway.
  • Wen X; Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI, USA.
  • Hornsby W; Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA.
  • Dewey FE; Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI, USA.
  • Boehnke M; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
  • Kheterpal S; Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.
  • Mukherjee B; Department of Medicine, Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway.
  • Lee S; Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.
  • Kang HM; Department of Cardiology, St. Olav's University Hospital, Trondheim University Hospital, Trondheim, Norway.
  • Holm H; deCODE genetics/Amgen, Inc., Reykjavik, Iceland.
  • Kitzman J; Regeneron Genetics Center, Tarrytown, NY, USA.
  • Shavit JA; Regeneron Genetics Center, Tarrytown, NY, USA.
  • Jalife J; deCODE genetics/Amgen, Inc., Reykjavik, Iceland.
  • Brummett CM; Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
  • Teslovich TM; Department of Medicine, Landspitali - National University Hospital, Reykjavik, Iceland.
  • Carey DJ; deCODE genetics/Amgen, Inc., Reykjavik, Iceland.
  • Gudbjartsson DF; Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
  • Stefansson K; Regeneron Genetics Center, Tarrytown, NY, USA.
  • Abecasis GR; Regeneron Genetics Center, Tarrytown, NY, USA.
  • Hveem K; Laboratory of Molecular Cardiology, Department of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
  • Willer CJ; Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.
Nat Genet ; 50(9): 1234-1239, 2018 09.
Article en En | MEDLINE | ID: mdl-30061737
ABSTRACT
To identify genetic variation underlying atrial fibrillation, the most common cardiac arrhythmia, we performed a genome-wide association study of >1,000,000 people, including 60,620 atrial fibrillation cases and 970,216 controls. We identified 142 independent risk variants at 111 loci and prioritized 151 functional candidate genes likely to be involved in atrial fibrillation. Many of the identified risk variants fall near genes where more deleterious mutations have been reported to cause serious heart defects in humans (GATA4, MYH6, NKX2-5, PITX2, TBX5)1, or near genes important for striated muscle function and integrity (for example, CFL2, MYH7, PKP2, RBM20, SGCG, SSPN). Pathway and functional enrichment analyses also suggested that many of the putative atrial fibrillation genes act via cardiac structural remodeling, potentially in the form of an 'atrial cardiomyopathy'2, either during fetal heart development or as a response to stress in the adult heart.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Fibrilación Atrial / Mutación Tipo de estudio: Etiology_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Nat Genet Asunto de la revista: GENETICA MEDICA Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Fibrilación Atrial / Mutación Tipo de estudio: Etiology_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Nat Genet Asunto de la revista: GENETICA MEDICA Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos