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Nielsen JB, Fritsche LG, Zhou W, et al. Genome-wide Study of Atrial Fibrillation Identifies Seven Risk Loci and Highlights Biological Pathways and Regulatory Elements Involved in Cardiac Development. Am J Hum Genet. 2017;102(1):103-115doi: 10.1016/j.ajhg.2017.12.003.
Nielsen, J. B., Fritsche, L. G., Zhou, W., Teslovich, T. M., Holmen, O. L., Gustafsson, S., Gabrielsen, M. E., Schmidt, E. M., Beaumont, R., Wolford, B. N., Lin, M., Brummett, C. M., Preuss, M. H., Refsgaard, L., Bottinger, E. P., Graham, S. E., Surakka, I., Chu, Y., Skogholt, A. H., Dalen, H., Boyle, A. P., Oral, H., Herron, T. J., Kitzman, J., Jalife, J., Svendsen, J. H., Olesen, M. S., Njølstad, I., Løchen, M. L., Baras, A., Gottesman, O., Marcketta, A., O'Dushlaine, C., Ritchie, M. D., Wilsgaard, T., Loos, R. J. F., Frayling, T. M., Boehnke, M., Ingelsson, E., Carey, D. J., Dewey, F. E., Kang, H. M., Abecasis, G. R., Hveem, K., & Willer, C. J. (2018). Genome-wide Study of Atrial Fibrillation Identifies Seven Risk Loci and Highlights Biological Pathways and Regulatory Elements Involved in Cardiac Development. American journal of human genetics, 102(1), 103-115. https://doi.org/10.1016/j.ajhg.2017.12.003
Nielsen, Jonas B, et al. "Genome-wide Study of Atrial Fibrillation Identifies Seven Risk Loci and Highlights Biological Pathways and Regulatory Elements Involved in Cardiac Development." American journal of human genetics vol. 102,1 (2018): 103-115. doi: https://doi.org/10.1016/j.ajhg.2017.12.003
Nielsen JB, Fritsche LG, Zhou W, Teslovich TM, Holmen OL, Gustafsson S, Gabrielsen ME, Schmidt EM, Beaumont R, Wolford BN, Lin M, Brummett CM, Preuss MH, Refsgaard L, Bottinger EP, Graham SE, Surakka I, Chu Y, Skogholt AH, Dalen H, Boyle AP, Oral H, Herron TJ, Kitzman J, Jalife J, Svendsen JH, Olesen MS, Njølstad I, Løchen ML, Baras A, Gottesman O, Marcketta A, O'Dushlaine C, Ritchie MD, Wilsgaard T, Loos RJF, Frayling TM, Boehnke M, Ingelsson E, Carey DJ, Dewey FE, Kang HM, Abecasis GR, Hveem K, Willer CJ. Genome-wide Study of Atrial Fibrillation Identifies Seven Risk Loci and Highlights Biological Pathways and Regulatory Elements Involved in Cardiac Development. Am J Hum Genet. 2018 Jan 04;102(1):103-115. doi: 10.1016/j.ajhg.2017.12.003. Epub 2017 Dec 28. PMID: 29290336; PMCID: PMC5777936.
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Am J Hum Genet. 2018 Jan 04;102(1):103-115. doi: 10.1016/j.ajhg.2017.12.003. Epub 2017 Dec 28.

Genome-wide Study of Atrial Fibrillation Identifies Seven Risk Loci and Highlights Biological Pathways and Regulatory Elements Involved in Cardiac Development.

American journal of human genetics

Jonas B Nielsen, Lars G Fritsche, Wei Zhou, Tanya M Teslovich, Oddgeir L Holmen, Stefan Gustafsson, Maiken E Gabrielsen, Ellen M Schmidt, Robin Beaumont, Brooke N Wolford, Maoxuan Lin, Chad M Brummett, Michael H Preuss, Lena Refsgaard, Erwin P Bottinger, Sarah E Graham, Ida Surakka, Yunhan Chu, Anne Heidi Skogholt, Håvard Dalen, Alan P Boyle, Hakan Oral, Todd J Herron, Jacob Kitzman, José Jalife, Jesper H Svendsen, Morten S Olesen, Inger Njølstad, Maja-Lisa Løchen, Aris Baras, Omri Gottesman, Anthony Marcketta, Colm O'Dushlaine, Marylyn D Ritchie, Tom Wilsgaard, Ruth J F Loos, Timothy M Frayling, Michael Boehnke, Erik Ingelsson, David J Carey, Frederick E Dewey, Hyun M Kang, Gonçalo R Abecasis, Kristian Hveem, Cristen J Willer

Affiliations

  1. Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI 48109, USA; Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
  2. HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger 7600, Norway; Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA; K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health, Norwegian University of Science and Technology, Trondheim 7491, Norway.
  3. Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA; Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
  4. Regeneron Genetics Center, Tarrytown, NY 10591, USA.
  5. HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger 7600, Norway; K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health, Norwegian University of Science and Technology, Trondheim 7491, Norway; Department of Cardiology, St. Olav's University Hospital, Trondheim 7030, Norway.
  6. Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala 75237, Sweden.
  7. HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger 7600, Norway; K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health, Norwegian University of Science and Technology, Trondheim 7491, Norway.
  8. Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
  9. Royal Devon & Exeter NHS Foundation Trust and University of Exeter Barrack Road Exeter, Exeter EX2 5WD, UK.
  10. Department of Anesthesiology, University of Michigan, Ann Arbor, MI 48109, USA.
  11. Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Genetics of Obesity and Related Metabolic Traits Program, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  12. Laboratory for Molecular Cardiology, Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen 2100, Denmark.
  13. Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Mindich Child Health Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
  14. Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
  15. Department of Cardiology, St. Olav's University Hospital, Trondheim 7030, Norway; Department of Medicine, Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger 7600, Norway; Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim 7491, Norway.
  16. Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA.
  17. Department of Internal Medicine, Center for Arrhythmia Research, University of Michigan, Ann Arbor, MI 48109, USA.
  18. Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA.
  19. Department of Internal Medicine, Center for Arrhythmia Research, University of Michigan, Ann Arbor, MI 48109, USA; Fundacion Centro Nacional de Investigaciones Cardiovasculares, Madrid 28029, Spain.
  20. Laboratory for Molecular Cardiology, Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen 2100, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark.
  21. Laboratory for Molecular Cardiology, Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen 2100, Denmark; Department of Biomedicine, University of Copenhagen, Copenhagen 2200, Denmark.
  22. Department of Community Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, Tromsø 9019, Norway.
  23. Geisinger Health System, Danville, PA 17822, USA.
  24. Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA; K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health, Norwegian University of Science and Technology, Trondheim 7491, Norway.
  25. Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala 75237, Sweden; Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA.
  26. HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger 7600, Norway; K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health, Norwegian University of Science and Technology, Trondheim 7491, Norway; Department of Medicine, Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger 7600, Norway. Electronic address: [email protected].
  27. Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI 48109, USA; Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA; Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA; K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health, Norwegian University of Science and Technology, Trondheim 7491, Norway; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: [email protected].

PMID: 29290336 PMCID: PMC5777936 DOI: 10.1016/j.ajhg.2017.12.003

Abstract

Atrial fibrillation (AF) is a common cardiac arrhythmia and a major risk factor for stroke, heart failure, and premature death. The pathogenesis of AF remains poorly understood, which contributes to the current lack of highly effective treatments. To understand the genetic variation and biology underlying AF, we undertook a genome-wide association study (GWAS) of 6,337 AF individuals and 61,607 AF-free individuals from Norway, including replication in an additional 30,679 AF individuals and 278,895 AF-free individuals. Through genotyping and dense imputation mapping from whole-genome sequencing, we tested almost nine million genetic variants across the genome and identified seven risk loci, including two novel loci. One novel locus (lead single-nucleotide variant [SNV] rs12614435; p = 6.76 × 10

Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Keywords: CDKN2C; DMRTA2; GWAS; TTN; atrial fibrillation; cardiomyopathy; fetal; genetic risk score; heart; pathway

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