Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression.

Autor: Wray NR; Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia. naomi.wray@uq.edu.au.; Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia. naomi.wray@uq.edu.au., Ripke S; Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.; Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.; Department of Psychiatry and Psychotherapy, Universitätsmedizin Berlin Campus Charité Mitte, Berlin, Germany., Mattheisen M; Department of Biomedicine, Aarhus University, Aarhus, Denmark.; iSEQ, Centre for Integrative Sequencing, Aarhus University, Aarhus, Denmark.; iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.; Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden., Trzaskowski M; Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia., Byrne EM; Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia., Abdellaoui A; Department of Biological Psychology and EMGO+ Institute for Health and Care Research, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands., Adams MJ; Division of Psychiatry, University of Edinburgh, Edinburgh, UK., Agerbo E; iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.; Centre for Integrated Register-Based Research, Aarhus University, Aarhus, Denmark.; National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark., Air TM; Discipline of Psychiatry, University of Adelaide, Adelaide, South Australia, Australia., Andlauer TMF; Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany.; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany., Bacanu SA; Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA., Bækvad-Hansen M; iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.; Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark., Beekman AFT; Department of Psychiatry, Vrije Universiteit Medical Center and GGZ inGeest, Amsterdam, The Netherlands., Bigdeli TB; Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA.; Virginia Institute for Psychiatric and Behavior Genetics, Richmond, VA, USA., Binder EB; Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany.; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA., Blackwood DRH; Division of Psychiatry, University of Edinburgh, Edinburgh, UK., Bryois J; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden., Buttenschøn HN; iSEQ, Centre for Integrative Sequencing, Aarhus University, Aarhus, Denmark.; iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.; Department of Clinical Medicine, Translational Neuropsychiatry Unit, Aarhus University, Aarhus, Denmark., Bybjerg-Grauholm J; iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.; Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark., Cai N; Statistical Genomics and Systems Genetics, European Bioinformatics Institute (EMBL-EBI), Cambridge, UK.; Human Genetics, Wellcome Trust Sanger Institute, Cambridge, UK., Castelao E; Department of Psychiatry, University Hospital of Lausanne, Prilly, Switzerland., Christensen JH; Department of Biomedicine, Aarhus University, Aarhus, Denmark.; iSEQ, Centre for Integrative Sequencing, Aarhus University, Aarhus, Denmark.; iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark., Clarke TK; Division of Psychiatry, University of Edinburgh, Edinburgh, UK., Coleman JIR; MRC Social Genetic and Developmental Psychiatry Centre, King's College London, London, UK., Colodro-Conde L; Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia., Couvy-Duchesne B; Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.; Centre for Advanced Imaging, University of Queensland, Brisbane, Queensland, Australia., Craddock N; Psychological Medicine, Cardiff University, Cardiff, UK., Crawford GE; Center for Genomic and Computational Biology, Duke University, Durham, NC, USA.; Department of Pediatrics, Division of Medical Genetics, Duke University, Durham, NC, USA., Crowley CA; Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Dashti HS; Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA., Davies G; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK., Deary IJ; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK., Degenhardt F; Institute of Human Genetics, University of Bonn, Bonn, Germany.; Life & Brain Center, Department of Genomics, University of Bonn, Bonn, Germany., Derks EM; Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia., Direk N; Psychiatry, Dokuz Eylul University School of Medicine, Izmir, Turkey.; Epidemiology, Erasmus MC, Rotterdam, The Netherlands., Dolan CV; Department of Biological Psychology and EMGO+ Institute for Health and Care Research, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands., Dunn EC; Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA, USA.; Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.; Psychiatric and Neurodevelopmental Genetics Unit (PNGU), Massachusetts General Hospital, Boston, MA, USA., Eley TC; MRC Social Genetic and Developmental Psychiatry Centre, King's College London, London, UK., Eriksson N; Research, 23andMe, Inc., Mountain View, CA, USA., Escott-Price V; Neuroscience and Mental Health, Cardiff University, Cardiff, UK., Kiadeh FHF; Bioinformatics, University of British Columbia, Vancouver, British Columbia, Canada., Finucane HK; Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA.; Department of Mathematics, Massachusetts Institute of Technology, Cambridge, MA, USA., Forstner AJ; Institute of Human Genetics, University of Bonn, Bonn, Germany.; Life & Brain Center, Department of Genomics, University of Bonn, Bonn, Germany.; Department of Psychiatry (UPK), University of Basel, Basel, Switzerland.; Human Genomics Research Group, Department of Biomedicine, University of Basel, Basel, Switzerland., Frank J; Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany., Gaspar HA; MRC Social Genetic and Developmental Psychiatry Centre, King's College London, London, UK., Gill M; Department of Psychiatry, Trinity College Dublin, Dublin, Ireland., Giusti-Rodríguez P; Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Goes FS; Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA., Gordon SD; Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia., Grove J; Department of Biomedicine, Aarhus University, Aarhus, Denmark.; iSEQ, Centre for Integrative Sequencing, Aarhus University, Aarhus, Denmark.; iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.; Bioinformatics Research Centre, Aarhus University, Aarhus, Denmark., Hall LS; Division of Psychiatry, University of Edinburgh, Edinburgh, UK.; Institute of Genetic Medicine, Newcastle University, Newcastle-upon-Tyne, UK., Hannon E; University of Exeter Medical School, Exeter, UK., Hansen CS; iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.; Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark., Hansen TF; Danish Headache Centre, Department of Neurology, Rigshospitalet, Glostrup, Denmark.; Institute of Biological Psychiatry, Mental Health Center Sct. Hans, Mental Health Services Capital Region of Denmark, Copenhagen, Denmark.; iPSYCH, Lundbeck Foundation Initiative for Psychiatric Research, Copenhagen, Denmark., Herms S; Institute of Human Genetics, University of Bonn, Bonn, Germany.; Life & Brain Center, Department of Genomics, University of Bonn, Bonn, Germany.; Human Genomics Research Group, Department of Biomedicine, University of Basel, Basel, Switzerland., Hickie IB; Brain and Mind Centre, University of Sydney, Sydney, New South Wales, Australia., Hoffmann P; Institute of Human Genetics, University of Bonn, Bonn, Germany.; Life & Brain Center, Department of Genomics, University of Bonn, Bonn, Germany.; Human Genomics Research Group, Department of Biomedicine, University of Basel, Basel, Switzerland., Homuth G; Interfaculty Institute for Genetics and Functional Genomics, Department of Functional Genomics, University Medicine and Ernst Moritz Arndt University Greifswald, Greifswald, Germany., Horn C; Roche Pharmaceutical Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche, Ltd, Basel, Switzerland., Hottenga JJ; Department of Biological Psychology and EMGO+ Institute for Health and Care Research, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands., Hougaard DM; iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.; Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, Denmark., Hu M; Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA., Hyde CL; Statistics, Pfizer Global Research and Development, Groton, CT, USA., Ising M; Max Planck Institute of Psychiatry, Munich, Germany., Jansen R; Department of Psychiatry, Vrije Universiteit Medical Center and GGZ inGeest, Amsterdam, The Netherlands., Jin F; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, USA.; Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH, USA., Jorgenson E; Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA., Knowles JA; Psychiatry and Behavioral Sciences, University of Southern California, Los Angeles, CA, USA., Kohane IS; Informatics Program, Boston Children's Hospital, Boston, MA, USA.; Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.; Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA., Kraft J; Department of Psychiatry and Psychotherapy, Universitätsmedizin Berlin Campus Charité Mitte, Berlin, Germany., Kretzschmar WW; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK., Krogh J; Department of Endocrinology at Herlev University Hospital, University of Copenhagen, Copenhagen, Denmark., Kutalik Z; Swiss Institute of Bioinformatics, Lausanne, Switzerland.; Institute of Social and Preventive Medicine (IUMSP), University Hospital of Lausanne, Lausanne, Switzerland., Lane JM; Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.; Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA., Li Y; Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK., Li Y; Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Lind PA; Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia., Liu X; Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH, USA., Lu L; Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH, USA., MacIntyre DJ; Mental Health, NHS 24, Glasgow, UK.; Division of Psychiatry, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK., MacKinnon DF; Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA., Maier RM; Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia., Maier W; Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany., Marchini J; Statistics, University of Oxford, Oxford, UK., Mbarek H; Department of Biological Psychology and EMGO+ Institute for Health and Care Research, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands., McGrath P; Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, USA., McGuffin P; MRC Social Genetic and Developmental Psychiatry Centre, King's College London, London, UK., Medland SE; Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia., Mehta D; Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.; School of Psychology and Counseling, Queensland University of Technology, Brisbane, Queensland, Australia., Middeldorp CM; Department of Biological Psychology and EMGO+ Institute for Health and Care Research, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.; Child and Youth Mental Health Service, Children's Health Queensland Hospital and Health Service, South Brisbane, Queensland, Australia.; Child Health Research Centre, University of Queensland, Brisbane, Queensland, Australia., Mihailov E; Estonian Genome Center, University of Tartu, Tartu, Estonia., Milaneschi Y; Department of Psychiatry, Vrije Universiteit Medical Center and GGZ inGeest, Amsterdam, The Netherlands., Milani L; Estonian Genome Center, University of Tartu, Tartu, Estonia., Mill J; University of Exeter Medical School, Exeter, UK., Mondimore FM; Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA., Montgomery GW; Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia., Mostafavi S; Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.; Statistics, University of British Columbia, Vancouver, British Columbia, Canada., Mullins N; MRC Social Genetic and Developmental Psychiatry Centre, King's College London, London, UK., Nauck M; DZHK (German Centre for Cardiovascular Research), partner site Greifswald, University Medicine, University Medicine Greifswald, Greifswald, Germany.; Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany., Ng B; Statistics, University of British Columbia, Vancouver, British Columbia, Canada., Nivard MG; Department of Biological Psychology and EMGO+ Institute for Health and Care Research, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands., Nyholt DR; Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia., O'Reilly PF; MRC Social Genetic and Developmental Psychiatry Centre, King's College London, London, UK., Oskarsson H; Humus, Reykjavik, Iceland., Owen MJ; MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK., Painter JN; Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia., Pedersen CB; iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.; Centre for Integrated Register-Based Research, Aarhus University, Aarhus, Denmark.; National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark., Pedersen MG; iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.; Centre for Integrated Register-Based Research, Aarhus University, Aarhus, Denmark.; National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark., Peterson RE; Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA.; Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA., Pettersson E; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden., Peyrot WJ; Department of Psychiatry, Vrije Universiteit Medical Center and GGZ inGeest, Amsterdam, The Netherlands., Pistis G; Department of Psychiatry, University Hospital of Lausanne, Prilly, Switzerland., Posthuma D; Complex Trait Genetics, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.; Clinical Genetics, Vrije Universiteit Medical Center, Amsterdam, The Netherlands., Purcell SM; Department of Psychiatry, Brigham and Women's Hospital, Boston, MA, USA., Quiroz JA; Solid Biosciences, Boston, MA, USA., Qvist P; Department of Biomedicine, Aarhus University, Aarhus, Denmark.; iSEQ, Centre for Integrative Sequencing, Aarhus University, Aarhus, Denmark.; iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark., Rice JP; Department of Psychiatry, Washington University in St. Louis School of Medicine, St. Louis, MO, USA., Riley BP; Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA., Rivera M; MRC Social Genetic and Developmental Psychiatry Centre, King's College London, London, UK.; Department of Biochemistry and Molecular Biology II, Institute of Neurosciences, Center for Biomedical Research, University of Granada, Granada, Spain., Saeed Mirza S; Epidemiology, Erasmus MC, Rotterdam, The Netherlands., Saxena R; Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.; Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.; Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA., Schoevers R; Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Schulte EC; Department of Psychiatry and Psychotherapy, Medical Center of the University of Munich, Campus Innenstadt, Munich, Germany.; Institute of Psychiatric Phenomics and Genomics (IPPG), Medical Center of the University of Munich, Campus Innenstadt, Munich, Germany., Shen L; Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA., Shi J; Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA., Shyn SI; Behavioral Health Services, Kaiser Permanente Washington, Seattle, WA, USA., Sigurdsson E; Faculty of Medicine, Department of Psychiatry, University of Iceland, Reykjavik, Iceland., Sinnamon GBC; School of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia., Smit JH; Department of Psychiatry, Vrije Universiteit Medical Center and GGZ inGeest, Amsterdam, The Netherlands., Smith DJ; Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK., Stefansson H; deCODE Genetics/Amgen, Inc., Reykjavik, Iceland., Steinberg S; deCODE Genetics/Amgen, Inc., Reykjavik, Iceland., Stockmeier CA; Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, MS, USA., Streit F; Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany., Strohmaier J; Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany., Tansey KE; College of Biomedical and Life Sciences, Cardiff University, Cardiff, UK., Teismann H; Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany., Teumer A; Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany., Thompson W; iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.; Institute of Biological Psychiatry, Mental Health Center Sct. Hans, Mental Health Services Capital Region of Denmark, Copenhagen, Denmark.; KG Jebsen Centre for Psychosis Research, Norway Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.; Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA., Thomson PA; Medical Genetics Section, CGEM, IGMM, University of Edinburgh, Edinburgh, UK., Thorgeirsson TE; deCODE Genetics/Amgen, Inc., Reykjavik, Iceland., Tian C; Research, 23andMe, Inc., Mountain View, CA, USA., Traylor M; Clinical Neurosciences, University of Cambridge, Cambridge, UK., Treutlein J; Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany., Trubetskoy V; Department of Psychiatry and Psychotherapy, Universitätsmedizin Berlin Campus Charité Mitte, Berlin, Germany., Uitterlinden AG; Internal Medicine, Erasmus MC, Rotterdam, The Netherlands., Umbricht D; Roche Pharmaceutical Research and Early Development, Neuroscience, Ophthalmology and Rare Diseases Discovery and Translational Medicine Area, Roche Innovation Center Basel, F. Hoffmann-La Roche, Ltd, Basel, Switzerland., Van der Auwera S; Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany., van Hemert AM; Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands., Viktorin A; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden., Visscher PM; Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.; Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia., Wang Y; iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.; Institute of Biological Psychiatry, Mental Health Center Sct. Hans, Mental Health Services Capital Region of Denmark, Copenhagen, Denmark.; KG Jebsen Centre for Psychosis Research, Norway Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway., Webb BT; Virginia Institute of Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA., Weinsheimer SM; iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.; Institute of Biological Psychiatry, Mental Health Center Sct. Hans, Mental Health Services Capital Region of Denmark, Copenhagen, Denmark., Wellmann J; Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany., Willemsen G; Department of Biological Psychology and EMGO+ Institute for Health and Care Research, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands., Witt SH; Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany., Wu Y; Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia., Xi HS; Computational Sciences Center of Emphasis, Pfizer Global Research and Development, Cambridge, MA, USA., Yang J; Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.; Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia., Zhang F; Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia., Arolt V; Department of Psychiatry, University of Münster, Munster, Germany., Baune BT; Discipline of Psychiatry, University of Adelaide, Adelaide, South Australia, Australia., Berger K; Institute of Epidemiology and Social Medicine, University of Münster, Münster, Germany., Boomsma DI; Department of Biological Psychology and EMGO+ Institute for Health and Care Research, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands., Cichon S; Institute of Human Genetics, University of Bonn, Bonn, Germany.; Human Genomics Research Group, Department of Biomedicine, University of Basel, Basel, Switzerland.; Institute of Neuroscience and Medicine (INM-1), Research Center Juelich, Juelich, Germany.; Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland., Dannlowski U; Department of Psychiatry, University of Münster, Munster, Germany., de Geus ECJ; Department of Biological Psychology and EMGO+ Institute for Health and Care Research, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.; Amsterdam Public Health Institute, Vrije Universiteit Medical Center, Amsterdam, The Netherlands., DePaulo JR; Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA., Domenici E; Centre for Integrative Biology, Università degli Studi di Trento, Trento, Italy., Domschke K; Department of Psychiatry and Psychotherapy, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Esko T; Medical and Population Genetics, Broad Institute, Cambridge, MA, USA.; Estonian Genome Center, University of Tartu, Tartu, Estonia., Grabe HJ; Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany., Hamilton SP; Psychiatry, Kaiser Permanente Northern California, San Francisco, CA, USA., Hayward C; MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK., Heath AC; Department of Psychiatry, Washington University in St. Louis School of Medicine, St. Louis, MO, USA., Hinds DA; Research, 23andMe, Inc., Mountain View, CA, USA., Kendler KS; Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA., Kloiber S; Max Planck Institute of Psychiatry, Munich, Germany.; Centre for Addiction and Mental Health, Toronto, Ontario, Canada.; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada., Lewis G; Division of Psychiatry, University College London, London, UK., Li QS; Neuroscience Therapeutic Area, Janssen Research and Development, LLC, Titusville, NJ, USA., Lucae S; Max Planck Institute of Psychiatry, Munich, Germany., Madden PFA; Department of Psychiatry, Washington University in St. Louis School of Medicine, St. Louis, MO, USA., Magnusson PK; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden., Martin NG; Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia., McIntosh AM; Division of Psychiatry, University of Edinburgh, Edinburgh, UK.; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK., Metspalu A; Estonian Genome Center, University of Tartu, Tartu, Estonia.; Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia., Mors O; iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.; Psychosis Research Unit, Aarhus University Hospital, Risskov, Aarhus, Denmark., Mortensen PB; iSEQ, Centre for Integrative Sequencing, Aarhus University, Aarhus, Denmark.; iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.; Centre for Integrated Register-Based Research, Aarhus University, Aarhus, Denmark.; National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark., Müller-Myhsok B; Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany.; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.; Institute of Translational Medicine, University of Liverpool, Liverpool, UK., Nordentoft M; iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.; Mental Health Center Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark., Nöthen MM; Institute of Human Genetics, University of Bonn, Bonn, Germany.; Life & Brain Center, Department of Genomics, University of Bonn, Bonn, Germany., O'Donovan MC; MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK., Paciga SA; Human Genetics and Computational Biomedicine, Pfizer Global Research and Development, Groton, CT, USA., Pedersen NL; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden., Penninx BWJH; Department of Psychiatry, Vrije Universiteit Medical Center and GGZ inGeest, Amsterdam, The Netherlands., Perlis RH; Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.; Psychiatry, Harvard Medical School, Boston, MA, USA., Porteous DJ; Medical Genetics Section, CGEM, IGMM, University of Edinburgh, Edinburgh, UK., Potash JB; Psychiatry, University of Iowa, Iowa City, IA, USA., Preisig M; Department of Psychiatry, University Hospital of Lausanne, Prilly, Switzerland., Rietschel M; Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany., Schaefer C; Division of Research, Kaiser Permanente Northern California, Oakland, CA, USA., Schulze TG; Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.; Psychiatry and Behavioral Sciences, Johns Hopkins University, Baltimore, MD, USA.; Institute of Psychiatric Phenomics and Genomics (IPPG), Medical Center of the University of Munich, Campus Innenstadt, Munich, Germany.; Human Genetics Branch, NIMH Division of Intramural Research Programs, Bethesda, MD, USA.; Department of Psychiatry and Psychotherapy, University Medical Center Göttingen, Göttingen, Germany., Smoller JW; Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA, USA.; Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.; Psychiatric and Neurodevelopmental Genetics Unit (PNGU), Massachusetts General Hospital, Boston, MA, USA., Stefansson K; deCODE Genetics/Amgen, Inc., Reykjavik, Iceland.; Faculty of Medicine, University of Iceland, Reykjavik, Iceland., Tiemeier H; Epidemiology, Erasmus MC, Rotterdam, The Netherlands.; Child and Adolescent Psychiatry, Erasmus MC, Rotterdam, The Netherlands.; Psychiatry, Erasmus MC, Rotterdam, The Netherlands., Uher R; Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada., Völzke H; Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany., Weissman MM; Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, USA.; Division of Epidemiology, New York State Psychiatric Institute, New York, NY, USA., Werge T; iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark.; Institute of Biological Psychiatry, Mental Health Center Sct. Hans, Mental Health Services Capital Region of Denmark, Copenhagen, Denmark.; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark., Winslow AR; Human Genetics and Computational Biomedicine, Pfizer Global Research and Development, Cambridge, MA, USA.; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA., Lewis CM; MRC Social Genetic and Developmental Psychiatry Centre, King's College London, London, UK.; Department of Medical and Molecular Genetics, King's College London, London, UK., Levinson DF; Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA., Breen G; MRC Social Genetic and Developmental Psychiatry Centre, King's College London, London, UK.; NIHR BRC for Mental Health, King's College London, London, UK., Børglum AD; Department of Biomedicine, Aarhus University, Aarhus, Denmark.; iSEQ, Centre for Integrative Sequencing, Aarhus University, Aarhus, Denmark.; iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark., Sullivan PF; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. pfsulliv@med.unc.edu.; Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. pfsulliv@med.unc.edu.; Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. pfsulliv@med.unc.edu.
Jazyk: angličtina
Zdroj: Nature genetics [Nat Genet] 2018 May; Vol. 50 (5), pp. 668-681. Date of Electronic Publication: 2018 Apr 26.
DOI: 10.1038/s41588-018-0090-3
Abstrakt: Major depressive disorder (MDD) is a common illness accompanied by considerable morbidity, mortality, costs, and heightened risk of suicide. We conducted a genome-wide association meta-analysis based in 135,458 cases and 344,901 controls and identified 44 independent and significant loci. The genetic findings were associated with clinical features of major depression and implicated brain regions exhibiting anatomical differences in cases. Targets of antidepressant medications and genes involved in gene splicing were enriched for smaller association signal. We found important relationships of genetic risk for major depression with educational attainment, body mass, and schizophrenia: lower educational attainment and higher body mass were putatively causal, whereas major depression and schizophrenia reflected a partly shared biological etiology. All humans carry lesser or greater numbers of genetic risk factors for major depression. These findings help refine the basis of major depression and imply that a continuous measure of risk underlies the clinical phenotype.
Databáze: MEDLINE