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

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Naomi R Wray, Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia. naomi.wray@uq.edu.au.
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  • Stephan Ripke, Department of Psychiatry and Psychotherapy, Charité Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany.
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  • Manuel Mattheisen
  • Maciej Trzaskowski, Queensland Brain Institute, University of Queensland, Brisbane, Australia; Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia.
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  • Enda M Byrne, Queensland Brain Institute, University of Queensland, Brisbane, Australia; Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia.
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  • Abdel Abdellaoui, Department of Biological Psychology, EMGO Institute for Health and Care Research and Neuroscience Campus Amsterdam, Vrije Universiteit, Amsterdam, The Netherlands.
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  • Mark J Adams, Division of Psychiatry, University of Edinburgh, Edinburgh, United Kingdom.
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  • Esben Agerbo
  • Tracy M Air, Discipline of Psychiatry, University of Adelaide, Adelaide, South Australia, Australia.
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  • Till M F Andlauer, 1] Statistical Genetics, Department of Translational Psychiatry, Max Planck Institute of Psychiatry, D-80804 Munich, Germany [2] Munich Cluster for Systems Neurology (SyNergy), D-80336 Munich, Germany [3] Institute of Translational Medicine, University of Liverpool, L69 3BX Liverpool, UK.
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  • Silviu-Alin Bacanu, Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA.
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  • Marie Bækvad-Hansen, Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, 2300, Denmark.
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  • Aartjan F T Beekman, Department of Psychiatry, Amsterdam Public Health and Amsterdam Neuroscience, Vrije Universiteit Medical Center and GGZ inGeest, Amsterdam, the Netherlands.
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  • Tim B Bigdeli, Virginia Institute for Psychiatric and Behavior Genetics, Richmond, VA, USA.
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  • Elisabeth B Binder, Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
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  • Douglas R H Blackwood, Division of Psychiatry, University of Edinburgh, Edinburgh, United Kingdom.
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  • Julien Bryois, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
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  • Henriette N Buttenschøn
  • Jonas Bybjerg-Grauholm, Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, 2300, Denmark.
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  • Na Cai, Human Genetics, Wellcome Trust Sanger Institute, Cambridge, UK.
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  • Enrique Castelao, Department of Psychiatry, University Hospital of Lausanne, Prilly, Switzerland.
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  • Jane Hvarregaard Christensen
  • Toni-Kim Clarke, Division of Psychiatry, University of Edinburgh, Edinburgh, United Kingdom.
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  • Jonathan I R Coleman, MRC Social, Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College London, London, UK.
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  • Lucía Colodro-Conde, Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
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  • Baptiste Couvy-Duchesne, Centre for Advanced Imaging, University of Queensland, Brisbane, QLD, Australia.
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  • Nick Craddock, Dept. of Psychological Medicine, School of Medicine, Cardiff University, Cardiff CF10 3XQ, UK
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  • Gregory E Crawford, Department of Pediatrics, Division of Medical Genetics, Duke University, Durham, NC, USA.
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  • Cheynna A Crowley, Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
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  • Hassan S Dashti, Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
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  • Gail Davies, Centre for Cognitive Ageing and Cognitive Epidemiology, Psychology, University of Edinburgh, Edinburgh, UK.
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  • Ian J Deary, Centre for Cognitive Ageing and Cognitive Epidemiology, Psychology, University of Edinburgh, Edinburgh, UK.
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  • Franziska Degenhardt, Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany ; Institute of Human Genetics, University of Bonn, Bonn, Germany ; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany.
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  • Eske M Derks, Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
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  • Nese Direk, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
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  • Conor V Dolan, Department of Biological Psychology, EMGO Institute for Health and Care Research and Neuroscience Campus Amsterdam, Vrije Universiteit, Amsterdam, The Netherlands.
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  • Erin C Dunn, Psychiatric and Neurodevelopmental Genetics Unit (PNGU), Massachusetts General Hospital, Boston, MA, USA.
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  • Thalia C Eley, MRC Social, Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College London, London, UK.
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  • Nicholas Eriksson, Research, 23andMe, Inc., Mountain View, CA, USA.
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  • Valentina Escott-Price, MRC Centre for Neuropsychiatric Genetics and Genomics, Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, United Kingdom.
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  • Jakob Grove
  • Christine Søholm Hansen, iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark, Center for Neonatal Screening, Department for Congenital Disorders, Statens Serum Institut, Copenhagen, 2300, Denmark.
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  • Thomas F Hansen, 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, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, DK-2100 Copenhagen, Denmark.
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  • Carsten Bøcker Pedersen
  • Marianne Giørtz Pedersen
  • Per Qvist
  • Jian Yang, Queensland Brain Institute, University of Queensland, Brisbane, Australia; Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia., Queensland Brain Institute, The University of Queensland, Brisbane, Australia
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  • Ole Mors
  • Preben Bo Mortensen
  • Merete Nordentoft, Copenhagen Research Center for Mental Health-CORE, Mental Health Centre Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark., Denmark
  • Thomas Werge, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Denmark
  • Anders D Børglum
  • Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium

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.

Original languageEnglish
JournalNature Genetics
Volume50
Issue5
Pages (from-to)668-681
Number of pages14
ISSN1061-4036
DOIs
Publication statusPublished - 2018

    Research areas

  • Case-Control Studies, Depressive Disorder, Major/genetics, Female, Genetic Predisposition to Disease, Genome-Wide Association Study/methods, Humans, Male, Multifactorial Inheritance, Phenotype, Polymorphism, Single Nucleotide, Risk Factors, Schizophrenia/genetics

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