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Nielsen JB, Thorolfsdottir RB, Fritsche LG, et al. Biobank-driven genomic discovery yields new insight into atrial fibrillation biology. Nat Genet. 2018;50(9):1234-1239doi: 10.1038/s41588-018-0171-3.
Nielsen, J. B., Thorolfsdottir, R. B., Fritsche, L. G., Zhou, W., Skov, M. W., Graham, S. E., Herron, T. J., McCarthy, S., Schmidt, E. M., Sveinbjornsson, G., Surakka, I., Mathis, M. R., Yamazaki, M., Crawford, R. D., Gabrielsen, M. E., Skogholt, A. H., Holmen, O. L., Lin, M., Wolford, B. N., Dey, R., Dalen, H., Sulem, P., Chung, J. H., Backman, J. D., Arnar, D. O., Thorsteinsdottir, U., Baras, A., O'Dushlaine, C., Holst, A. G., Wen, X., Hornsby, W., Dewey, F. E., Boehnke, M., Kheterpal, S., Mukherjee, B., Lee, S., Kang, H. M., Holm, H., Kitzman, J., Shavit, J. A., Jalife, J., Brummett, C. M., Teslovich, T. M., Carey, D. J., Gudbjartsson, D. F., Stefansson, K., Abecasis, G. R., Hveem, K., & Willer, C. J. (2018). Biobank-driven genomic discovery yields new insight into atrial fibrillation biology. Nature genetics, 50(9), 1234-1239. https://doi.org/10.1038/s41588-018-0171-3
Nielsen, Jonas B, et al. "Biobank-driven genomic discovery yields new insight into atrial fibrillation biology." Nature genetics vol. 50,9 (2018): 1234-1239. doi: https://doi.org/10.1038/s41588-018-0171-3
Nielsen JB, Thorolfsdottir RB, Fritsche LG, Zhou W, Skov MW, Graham SE, Herron TJ, McCarthy S, Schmidt EM, Sveinbjornsson G, Surakka I, Mathis MR, Yamazaki M, Crawford RD, Gabrielsen ME, Skogholt AH, Holmen OL, Lin M, Wolford BN, Dey R, Dalen H, Sulem P, Chung JH, Backman JD, Arnar DO, Thorsteinsdottir U, Baras A, O'Dushlaine C, Holst AG, Wen X, Hornsby W, Dewey FE, Boehnke M, Kheterpal S, Mukherjee B, Lee S, Kang HM, Holm H, Kitzman J, Shavit JA, Jalife J, Brummett CM, Teslovich TM, Carey DJ, Gudbjartsson DF, Stefansson K, Abecasis GR, Hveem K, Willer CJ. Biobank-driven genomic discovery yields new insight into atrial fibrillation biology. Nat Genet. 2018 Sep;50(9):1234-1239. doi: 10.1038/s41588-018-0171-3. Epub 2018 Jul 30. PMID: 30061737; PMCID: PMC6530775.
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Nat Genet. 2018 Sep;50(9):1234-1239. doi: 10.1038/s41588-018-0171-3. Epub 2018 Jul 30.

Biobank-driven genomic discovery yields new insight into atrial fibrillation biology.

Nature genetics

Jonas B Nielsen, Rosa B Thorolfsdottir, Lars G Fritsche, Wei Zhou, Morten W Skov, Sarah E Graham, Todd J Herron, Shane McCarthy, Ellen M Schmidt, Gardar Sveinbjornsson, Ida Surakka, Michael R Mathis, Masatoshi Yamazaki, Ryan D Crawford, Maiken E Gabrielsen, Anne Heidi Skogholt, Oddgeir L Holmen, Maoxuan Lin, Brooke N Wolford, Rounak Dey, Håvard Dalen, Patrick Sulem, Jonathan H Chung, Joshua D Backman, David O Arnar, Unnur Thorsteinsdottir, Aris Baras, Colm O'Dushlaine, Anders G Holst, Xiaoquan Wen, Whitney Hornsby, Frederick E Dewey, Michael Boehnke, Sachin Kheterpal, Bhramar Mukherjee, Seunggeun Lee, Hyun M Kang, Hilma Holm, Jacob Kitzman, Jordan A Shavit, José Jalife, Chad M Brummett, Tanya M Teslovich, David J Carey, Daniel F Gudbjartsson, Kari Stefansson, Gonçalo R Abecasis, Kristian Hveem, Cristen J Willer

Affiliations

  1. Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI, USA.
  2. Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA.
  3. deCODE genetics/Amgen, Inc., Reykjavik, Iceland.
  4. Faculty of Medicine, University of Iceland, Reykjavik, Iceland.
  5. HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway.
  6. K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health, Norwegian University of Science and Technology, Trondheim, Norway.
  7. Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
  8. Laboratory of Molecular Cardiology, Department of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
  9. Department of Internal Medicine, Center for Arrhythmia Research, University of Michigan, Ann Arbor, MI, USA.
  10. Regeneron Genetics Center, Tarrytown, NY, USA.
  11. Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.
  12. Department of Anesthesiology, University of Michigan, Ann Arbor, MI, USA.
  13. Medical Device Development and Regulation Research Center, The University of Tokyo, Tokyo, Japan.
  14. Department of Cardiology, St. Olav's University Hospital, Trondheim, Norway.
  15. Department of Medicine, Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway.
  16. Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.
  17. Department of Cardiology, St. Olav's University Hospital, Trondheim University Hospital, Trondheim, Norway.
  18. Department of Medicine, Landspitali - National University Hospital, Reykjavik, Iceland.
  19. Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI, USA.
  20. Fundación Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
  21. Geisinger Health System, Danville, PA, USA.
  22. School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland.
  23. K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health, Norwegian University of Science and Technology, Trondheim, Norway. [email protected].
  24. Department of Biostatistics, Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA. [email protected].
  25. HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Levanger, Norway. [email protected].
  26. K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health, Norwegian University of Science and Technology, Trondheim, Norway. [email protected].
  27. Department of Medicine, Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway. [email protected].
  28. Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI, USA. [email protected].
  29. Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA. [email protected].
  30. Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA. [email protected].

PMID: 30061737 PMCID: PMC6530775 DOI: 10.1038/s41588-018-0171-3

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)

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