Journal article
Genome-wide Association for Major Depression Through Age at Onset Stratification: Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium.
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Power RA
Institute of Psychiatry, Psychology, and Neuroscience, King׳s College London, London.
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Tansey KE
MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, United Kingdom.
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Buttenschøn HN
Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus University, Aarhus, Denmark; Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
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Cohen-Woods S
Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, Australia.
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Bigdeli T
Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia.
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Hall LS
Division of Psychiatry, University of Edinburgh, Edinburgh, United Kingdom.
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Kutalik Z
Institute of Social and Preventive Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
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Lee SH
Queensland Brain Institute, The University of Queensland, Brisbane, Queensland; School of Environmental and Rural Science, University of New England, Armidale, New South Wales, Australia.
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Ripke S
Stanley Center for Psychiatric Research, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge; Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Department of Psychiatry and Psychotherapy, Charité, Campus Mitte, Berlin, Germany.
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Steinberg S
deCODE Genetics, Reykjavik, Iceland.
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Teumer A
Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
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Viktorin A
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
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Wray NR
Queensland Brain Institute, The University of Queensland, Brisbane, Queensland.
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Arolt V
Department of Psychiatry and Psychotherapy, University of Muenster, Muenster, Germany.
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Baune BT
Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, Australia.
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Boomsma DI
Department of Biological Psychology, EMGO Institute for Health and Care Research and Neuroscience Campus Amsterdam, Vrije Universiteit, Amsterdam, The Netherlands.
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Børglum AD
Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus University, Aarhus, Denmark; Department of Biomedicine and Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark.
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Byrne EM
Queensland Brain Institute, The University of Queensland, Brisbane, Queensland.
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Castelao E
Department of Psychiatry, Lausanne University Hospital, Lausanne, Switzerland.
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Craddock N
MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, United Kingdom.
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Craig IW
Institute of Psychiatry, Psychology, and Neuroscience, King׳s College London, London.
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Dannlowski U
Department of Psychiatry and Psychotherapy, University of Muenster, Muenster, Germany; Department of Psychiatry, University of Marburg, Marburg, Germany.
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Deary IJ
Centre for Cognitive Ageing and Cognitive Epidemiology, Edinburgh, United Kingdom; Department of Psychology, University of Edinburgh, Edinburgh, United Kingdom.
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Degenhardt F
Institute of Human Genetics; Bonn, Germany; Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany.
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Forstner AJ
Institute of Human Genetics; Bonn, Germany; Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany.
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Gordon SD
QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
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Grabe HJ
Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
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Grove J
Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus University, Aarhus, Denmark; Department of Biomedicine and Centre for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark.
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Hamilton SP
Department of Psychiatry, Kaiser Permanente San Francisco Medical Center, San Francisco, California.
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Hayward C
Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
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Heath AC
Department of Psychiatry, Washington University St. Louis, St. Louis, Missouri.
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Hocking LJ
Division of Applied Health Sciences, University of Aberdeen, Aberdeen, United Kingdom.
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Homuth G
Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Greifswald.
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Hottenga JJ
Department of Biological Psychology, EMGO Institute for Health and Care Research and Neuroscience Campus Amsterdam, Vrije Universiteit, Amsterdam, The Netherlands.
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Kloiber S
Max Planck Institute of Psychiatry, Munich, Germany.
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Krogh J
Mental Health Center Copenhagen, Mental Health Services in Capital Region, University of Copenhagen, Copenhagen, Denmark.
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Landén M
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.
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Lang M
Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
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Levinson DF
Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California.
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Lichtenstein P
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
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Lucae S
Max Planck Institute of Psychiatry, Munich, Germany.
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MacIntyre DJ
Division of Psychiatry, University of Edinburgh, Edinburgh, United Kingdom.
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Madden P
Department of Psychiatry, Washington University St. Louis, St. Louis, Missouri.
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Magnusson PKE
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
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Martin NG
QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
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McIntosh AM
Division of Psychiatry, University of Edinburgh, Edinburgh, United Kingdom; Centre for Cognitive Ageing and Cognitive Epidemiology, Edinburgh, United Kingdom.
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Middeldorp CM
Department of Biological Psychology, EMGO Institute for Health and Care Research and Neuroscience Campus Amsterdam, Vrije Universiteit, Amsterdam, The Netherlands.
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Milaneschi Y
Department of Psychiatry, EMGO Institute for Health and Care Research and Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
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Montgomery GW
QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
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Mors O
Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus University, Aarhus, Denmark; Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark.
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Müller-Myhsok B
Max Planck Institute of Psychiatry, Munich, Germany; Munich Cluster for Systems Neurology, Munich, Germany; Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.
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Nyholt DR
Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.
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Oskarsson H
Therapeia, Reykjavik, Iceland.
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Owen MJ
MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, United Kingdom.
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Padmanabhan S
Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom.
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Penninx BWJH
Department of Psychiatry, EMGO Institute for Health and Care Research and Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
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Pergadia ML
Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, Florida.
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Porteous DJ
Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
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Potash JB
Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa.
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Preisig M
Department of Psychiatry, Lausanne University Hospital, Lausanne, Switzerland.
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Rivera M
Institute of Psychiatry, Psychology, and Neuroscience, King׳s College London, London; CIBERSAM-Universidad de Granada e Instituto de Investigación Biosanitaria ibs, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain.
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Shi J
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
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Shyn SI
Department of Psychiatry, Group Health, Seattle, Washington.
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Sigurdsson E
University of Iceland; Department of Psychiatry, Landspitali University Hospital, Reykjavik, Iceland.
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Smit JH
Department of Psychiatry, EMGO Institute for Health and Care Research and Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
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Smith BH
Division of Population Health Sciences, University of Dundee, Dundee, United Kingdom.
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Stefansson H
deCODE Genetics, Reykjavik, Iceland.
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Stefansson K
deCODE Genetics, Reykjavik, Iceland.
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Strohmaier J
Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
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Sullivan PF
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
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Thomson P
Centre for Cognitive Ageing and Cognitive Epidemiology, Edinburgh, United Kingdom; Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
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Thorgeirsson TE
deCODE Genetics, Reykjavik, Iceland.
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Van der Auwera S
Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
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Weissman MM
College of Physicians and Surgeons and the Mailman School of Public Health, Columbia University and New York State Psychiatric Institute, New York, New York.
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Breen G
Institute of Psychiatry, Psychology, and Neuroscience, King׳s College London, London. Electronic address: cathryn.lewis@kcl.ac.uk.
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Lewis CM
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Published in:
- Biological psychiatry. - 2017
English
BACKGROUND
Major depressive disorder (MDD) is a disabling mood disorder, and despite a known heritable component, a large meta-analysis of genome-wide association studies revealed no replicable genetic risk variants. Given prior evidence of heterogeneity by age at onset in MDD, we tested whether genome-wide significant risk variants for MDD could be identified in cases subdivided by age at onset.
METHODS
Discovery case-control genome-wide association studies were performed where cases were stratified using increasing/decreasing age-at-onset cutoffs; significant single nucleotide polymorphisms were tested in nine independent replication samples, giving a total sample of 22,158 cases and 133,749 control subjects for subsetting. Polygenic score analysis was used to examine whether differences in shared genetic risk exists between earlier and adult-onset MDD with commonly comorbid disorders of schizophrenia, bipolar disorder, Alzheimer's disease, and coronary artery disease.
RESULTS
We identified one replicated genome-wide significant locus associated with adult-onset (>27 years) MDD (rs7647854, odds ratio: 1.16, 95% confidence interval: 1.11-1.21, p = 5.2 × 10-11). Using polygenic score analyses, we show that earlier-onset MDD is genetically more similar to schizophrenia and bipolar disorder than adult-onset MDD.
CONCLUSIONS
We demonstrate that using additional phenotype data previously collected by genetic studies to tackle phenotypic heterogeneity in MDD can successfully lead to the discovery of genetic risk factor despite reduced sample size. Furthermore, our results suggest that the genetic susceptibility to MDD differs between adult- and earlier-onset MDD, with earlier-onset cases having a greater genetic overlap with schizophrenia and bipolar disorder.
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Language
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Open access status
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hybrid
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Persistent URL
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https://sonar.ch/global/documents/283413
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