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Quantifying the Impact of Rare and Ultra-rare Coding Variation across the Phenotypic Spectrum
Authors:Andrea Ganna  F. Kyle Satterstrom  Seyedeh M. Zekavat  Indraniel Das  Mitja I. Kurki  Claire Churchhouse  Jessica Alfoldi  Alicia R. Martin  Aki S. Havulinna  Andrea Byrnes  Wesley K. Thompson  Philip R. Nielsen  Konrad J. Karczewski  Elmo Saarentaus  Manuel A. Rivas  Namrata Gupta  Olli Pietiläinen  Connor A. Emdin  Benjamin M. Neale
Affiliation:1. Analytic and Translational Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA;2. Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA;3. Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA;4. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm 17176, Sweden;5. Center for Genomic Medicine, Massachusetts General Hospital and Department of Medicine, Harvard Medical School, Boston, MA 02114, USA;6. McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO 63108, USA;7. Department of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI 48109, USA;8. Institute for Molecular Medicine Finland, FIMM, University of Helsinki, Helsinki 00290, Finland;9. Department of Psychiatry, University of California, San Diego, CA 94143, USA;10. Institute of Biological Psychiatry, MHC Sct. Hans, Mental Health Services Copenhagen, Roskilde 4000, Denmark;11. The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Denmark;12. KG Jebsen Centre for Psychosis Research, Norway Division of Mental Health and Addiction, Oslo University Hospital, Oslo 0318, Norway;13. National Centre for Register-based Research, School of Business and Social Sciences, Aarhus University, Aarhus 8210, Denmark;14. Centre for Integrated Register-based Research, Aarhus University, Aarhus 8210, Denmark;15. Department of Biomedical Data Science, Stanford University, Stanford, CA 94305, USA;16. Department of Stem Cell and Regenerative Biology, University of Harvard, Cambridge, MA 02138, USA;17. iSEQ, Center for Integrative Sequencing, Aarhus University, Aarhus 8210, Denmark;18. Department of Biomedicine - Human Genetics, Aarhus University, Aarhus 8210, Denmark;19. Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen 2300, Denmark;20. Programs in Metabolism and Medical & Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA;21. Diabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA;22. Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio 70211, Finland;23. Department of Health, THL-National Institute for Health and Welfare, Helsinki 00271, Finland;24. Department of Public Health, University of Helsinki, Helsinki 00014, Finland;25. Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK;26. Department of Clinical Genetics, Oulu University Hospital, Medical Research Center Oulu and PEDEGO Research Unit, University of Oulu, Oulu 90029, Finland;27. Mental Health Services in the Capital Region of Denmark, Mental Health Center Copenhagen, University of Copenhagen, Copenhagen 2100, Denmark;28. Psychosis Research Unit, Aarhus University Hospital, Risskov 8240, Denmark;29. Department of Clinical Medicine, University of Copenhagen, Copenhagen 2200, Denmark;30. Departments of Genetics and Psychiatry, University of North Carolina, Chapel Hill, NC 27599, USA
Abstract:
Keywords:exome sequencing  ultra-rare variants  rare variants  phewas  constraint genes  burden analysis  selection
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