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Estimating clinical risk in gene regions from population sequencing cohort data
Institution:1. Division of Genetics, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA;2. Harvard Medical School, Boston, MA, USA;1. Institute for Molecular Medicine Finland, FIMM, HiLIFE, University of Helsinki, Helsinki, Finland;2. Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA;3. Clinicum, Department of Public Health, University of Helsinki, Helsinki, Finland;4. Department of Epidemiology and Public Health, University College London, London, UK;5. Broad Institute of MIT and Harvard, Cambridge, MA, USA;6. Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA;1. Rady Children’s Institute for Genomic Medicine, San Diego, CA 92123, USA;2. Rady Children’s Hospital, San Diego, CA 92123, USA;3. Keck Graduate Institute, Claremont, CA 91711, USA;4. Illumina, Inc., San Diego, CA 92122, USA;5. Alexion, Astra Zeneca Rare Disease, Boston, MA 02210, USA;6. Department of Pediatrics, University of California San Diego, San Diego, CA 92093, USA;7. Fabric Genomics, Inc., Oakland, CA 94612, USA;8. Mass General Brigham, Broad Institute, Ariadne Labs and Harvard Medical School, Boston, MA 02115, USA;9. Genomenon, Inc., Ann Arbor, MI 48108, USA;10. TileDB, Inc., Cambridge, MA 02142, USA;11. Luna PBC, Inc., San Diego, CA 92121, USA;1. National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, GA, USA;2. Division of Laboratory Services, Newborn Screening and Molecular Biology Branch, Centers for Disease Control and Prevention, Atlanta, GA, USA;3. Association of Public Health Laboratories, Silver Spring, MD, USA;4. Department of Pediatrics, Nationwide Children’s Hospital, Columbus, OH, USA;5. Center for Public Health Innovation, CI International, Littleton, CO, USA;1. National Institutes of Health Undiagnosed Diseases Program, Common Fund, Office of the Director, National Institutes of Health, Bethesda, MD, USA;2. APHP.Nord, Robert Debré University Hospital, Department of Genetics, Paris, France;3. Université Paris Cité, Inserm UMR 1141, NeuroDiderot, 75019 Paris, France;4. Center for Rare Childhood Disorders, The Translational Genomics Research Institute, Phoenix, AZ, USA;5. Section of Pediatric Neurology and Developmental Neuroscience, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA;6. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA;7. Texas Children’s Hospital, Houston, TX, USA;8. Department of Rare Disease Genomics, Yokohama City University Hospital, Yokohama, Japan;9. Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan;10. Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands;11. Department of Pediatrics, Emma Children’s Hospital, Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam University Medical Centers, Amsterdam, the Netherlands;12. United for Metabolic Diseases, Amsterdam, the Netherlands;13. Department of Neuropediatrics, Tokyo Metropolitan Neurological Hospital, Tokyo, Japan;14. Department of Pediatrics, Shimada Ryoiku Medical Center Hachioji for Challenged Children, Tokyo, Japan;15. Amsterdam Leukodystrophy Center, Department of Child Neurology, Emma Children’s Hospital, Amsterdam University Medical Centers, and Amsterdam Neuroscience, Cellular & Molecular Mechanisms, Vrije Universiteit, Amsterdam, the Netherlands;16. Bioinformatics and Computational Biosciences Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA;17. Service de Neurologie Pédiatrique, DMU INOV-RDB, APHP, Hôpital Robert Debré, Paris, France;18. Department of Genetics, APHP-Robert Debré University Hospital, Paris, France;19. Laboratoire de biologie médicale multisites Seqoia - FMG2025, Paris, France;20. INSERM UMR1141, Neurodiderot, University of Paris, Paris, France;21. Service de Génétique Médicale, CHU Nantes, Nantes, France;22. Inserm, CNRS, University Nantes, l’institut du thorax, Nantes, France;23. APHP.Nord, Louis Mourier Hospital, Pediatrics Department, Paris, France;24. Laboratory of Medical Genetics, Translational Cytogenomics Research Unit, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy;25. Medical Genetics Unit, Bambino Gesù Children Hospital, IRCCS, Rome, Italy;26. Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA;27. Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA;28. Department of Diagnostic Radiology and Imaging, Children’s National Hospital, Washington, DC, USA;29. Office of the Clinical Director, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA;30. Human Biochemical Genetics Section, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA;1. Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Carlton, VIC 3053, Australia;2. Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK;3. Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC 3168, Australia;4. Murdoch Children’s Research Institute, Royal Children’s Hospital, Parkville, VIC 3051, Australia;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
Abstract:
Keywords:clinical risk prediction  genic regions  selective constraint  variant interpretation  variants of uncertain significance  predispositional cancer risk  breast cancer  missense variant prediction
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