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Evidence of epistasis in regions of long-range linkage disequilibrium across five complex diseases in the UK Biobank and eMERGE datasets
Affiliation:1. Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA;2. Department of Human Genetics, Katholieke Universiteit Leuven, ON4 Herestraat 49, 3000 Leuven, Belgium;3. Laboratory of Genetics, School of Medicine and Public Health, University of Wisconsin, Madison, WI 53706, USA;4. Columbia University, New York, NY 10027, USA;5. Genentech, San Francisco, CA 94080, USA;6. Mayo Clinic, Rochester, MN 55902, USA;7. Children’s Hospital of Pennsylvania, Philadelphia, PA 19104, USA;8. Department of Computational Biomedicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA;9. Department of Genetics and Genome Sciences, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA;10. Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA;1. Pacific Northwest Research Institute, Seattle, WA, USA;2. Department of Applied Mathematics, University of Washington, Seattle, WA, USA;3. Center for Genetic Medicine Research, Children’s National Research Institute, Children’s National Hospital, Washington, DC, USA;4. Department of Genomics and Precision Medicine, School of Medicine and Health Sciences, The George Washington University, Washington, DC, USA;5. Department of Neurology, Division of Neurogenetics and Neurodevelopmental Disabilities, Children’s National Hospital, Washington, DC, USA;6. Center for Neuroscience Research, Children’s National Research Institute, Children’s National Hospital, Washington, DC, USA;1. Department of Molecular Medicine, University of Pavia, Pavia, Italy;2. Section of Pediatric Neurology and Developmental Neuroscience, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA;3. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA;4. Texas Children’s Hospital, Houston, TX, USA;5. Molecular Diagnostics and Clinical Genetics Unit, Hospital Universitari Son Espases, Palma, Illes Balears, Spain;6. Genomics of Health, Institute of Health Research of the Balearic Islands, Palma, Illes Balears, Spain;7. Genetics Institute, Rambam Health Care Campus, Haifa, Israel;8. The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel;9. AP-HP, Service de Génétique Moléculaire Neurovasculaire, Hôpital Saint-Louis, Paris, France;10. Université de Paris, INSERM UMR-1141 Neurodiderot, Paris, France;11. Institute of Medical Genetics, University of Zurich, Schlieren-Zurich, Switzerland;12. Izmir Biomedicine and Genome Center, Dokuz Eylul University Health Campus, Izmir 35340, Turkey;13. Izmir International Biomedicine and Genome Institute, Dokuz Eylul University, Izmir 35340, Turkey;14. Department of Medical Biology, School of Medicine, Dokuz Eylul University, Izmir 35340, Turkey;15. The Genetic Institute, Emek Medical Center, Afula, Israel;16. Center for the Study of Myelofibrosis, Laboratory of Biochemistry, Biotechnology and Advanced Diagnosis, IRCCS Policlinico San Matteo Foundation, Pavia, Italy;17. Pathology Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy;18. Laboratory of Biochemistry-Biotechnology and Advanced Diagnostics, IRCCS Policlinico San Matteo Foundation, Pavia, Italy;19. Medical Genetics Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy;20. Neuroradiology Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy;21. Ophthalmology Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy;22. Child Neurology and Psychiatry Unit, Azienda USL-IRCCS di Reggio Emilia, Reggio Emilia, Italy;23. Department of Pediatrics, Faculty of Medicine, Kuwait University, P.O. Box 24923, Safat 13110, Kuwait;24. Tertiary ROP Center, Health Science University Kanuni Sultan Suleyman Training and Research Hospital, Istanbul 34303, Turkey;25. Department of Medical Genetics, Basaksehir Cam and Sakura City Hospital, Istanbul 34480, Turkey;26. Metabolic Pathologies and Pediatric Neurology Unit, Pediatric Service, Hospital Universitari Son Espases, Palma, Illes Balears, Spain;27. Pediatric Radiology Unit, Radiology Service, Hospital Universitari Son Espases, Palma, Illes Balears, Spain;28. Neurobiology, Institute of Health Research of the Balearic Islands, Palma, Illes Balears, Spain;29. Department of Radiology, Division of Pediatric Radiology, Dana Children’s Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv University, Tel Aviv, Israel;30. Sackler School of Medicine, Tel Aviv University, Tel-Aviv, Israel;31. AP-HM, Service de Génétique, Hôpital de la Timone, Marseille, France;32. Medical Genetics Service, CHUV, University of Lausanne, Lausanne, Switzerland;33. Inonu University, Faculty of Medicine, Turgut Ozal Research Center, Department of Pediatric Neurology, Malatya, Turkey;34. Department of Pediatric Neurology, School of Medicine, Dokuz Eylul University, Izmir 35340, Turkey;35. Department of Pediatrics B, Emek Medical Center, Afula, Israel;36. Poriya Medical Center and the Azrieli Faculty of Medicine, Bar-Ilan University, Ramat-Gan, Israel;37. Department of Biomedical Engineering, Tufts University, Medford, MA, USA;38. Department of Clinical Neurosciences, School of Clinical Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge CB2 0PY, UK;39. Department of Clinical Neurosciences, John Van Geest Centre for Brain Repair, School of Clinical Medicine, University of Cambridge, Cambridge CB2 0PY, UK;40. Children’s Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON K1H 8L1, Canada;41. Brain and Mind Research Institute, University of Ottawa, Ottawa ON K1H 8L1, Canada;42. Division of Neurology, Department of Medicine, The Ottawa Hospital, Ottawa, ON K1H 8L1, Canada;43. University Children’s Hospital Zurich, University of Zurich, Zurich, Switzerland;44. Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA;45. Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA;46. Neurogenetics Research Center, IRCCS Mondino Foundation, Pavia, Italy;1. Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, USA;2. Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA;3. Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA;4. VA Cooperative Studies Program Clinical Epidemiology Research Center (CSP-CERC), VA CT Healthcare System, West Haven, CT, USA;5. Department of Anthropology, University of Toronto, Mississauga, ON, Canada;6. Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada;7. Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA;8. Center for Innovations in Quality, Effectiveness, and Safety (IQuESt), Michael E. DeBakey VA Medical Center, Houston, TX 77030, USA;9. Department of Biostatistics and Bioinformatics, Duke University, Durham, NC 27705, USA;10. VA Cooperative Studies Program Epidemiology Center-Durham, Department of Veterans Affairs, Durham, NC 27705, USA;11. Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO, USA;12. Institute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA;1. Institute of Human Genetics, University Hospital of Cologne, University Cologne, Kerpener Str. 34, 50931 Cologne, Germany;2. Center for Molecular Medicine Cologne, University of Cologne, 50931 Cologne, Germany;3. Institute for Genetics, University of Cologne, 50674 Cologne, Germany;4. Cologne Center for Genomics and West German Genome Center, University of Cologne, 50931 Cologne, Germany;5. INSERM/ UEVE UMR 861, Université Paris Saclay, I-STEM, 91100 Corbeil-Essonnes, France;6. Center for Rare Diseases, University Hospital of Cologne, 50931 Cologne, Germany;1. Cancer Genetics Laboratory, Division of Pulmonary and Critical Care Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA;2. Division of Hematology/Oncology, Cancer and Blood Disease Institute, Children’s Hospital Los Angeles, Los Angeles, CA 90027, USA;3. Boston Dermatology and Laser Center, Massachusetts General Hospital, Boston, MA 02114, USA;4. Center for Cancer Genomics, Dana-Farber Cancer Institute, Boston, MA 02215, USA;5. Molecular Biology Core Facilities, Dana-Farber Cancer Institute, Boston, MA 02215, USA;6. Department of Dermatology, Uniformed Services University, Bethesda, MA 20814, USA;7. Pulmonary Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA;8. Department of Dermatology, University Hospitals Cleveland Medical Center, Case Western Reserve University Cleveland, Cleveland, OH 44106, USA;9. Division of Hospital Medicine, Barnes Jewish Hospital, Washington University in St Louis, St. Louis, MO 63110, USA;10. Department of Neurology and Epileptology, Children’s Memorial Health Institute, Warsaw 04-736, Poland;11. Research Department, Children’s Memorial Health Institute, Warsaw 04-736, Poland;1. The Center of Joint and Sports Medicine, Orthopedics Department, Zhongda Hospital, Southeast University, Nanjing, China
Abstract:
Keywords:epistasis  linkage disequilibrium  long-range  complex human disease  variable expressivity  pleiotropy  essential genes  evolution  interchromosomal
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