Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
27519822
TITLE
Genome-wide Association for Major Depression Through Age at Onset Stratification: Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium.
ABSTRACT
BACKGROUND NlmCategory: 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 NlmCategory: 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 NlmCategory: 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 NlmCategory: 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.
Copyright 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
DATE PUBLISHED
2016 May 24
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2015/12/01
revised 2016/03/26
accepted 2016/05/05
entrez 2016/08/14 06:00
pubmed 2016/08/16 06:00
medline 2016/08/16 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Power RA Power Robert A RA Institute of Psychiatry, Psychology, and Neuroscience, King׳s College London, London.
Tansey KE Tansey Katherine E KE MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, United Kingdom.
Buttenschøn HN Buttenschøn Henriette Nørmølle HN Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus University, Aarhus, Denmark; Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
Cohen-Woods S Cohen-Woods Sarah S Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, Australia.
Bigdeli T Bigdeli Tim T Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia.
Hall LS Hall Lynsey S LS Division of Psychiatry, University of Edinburgh, Edinburgh, United Kingdom.
Kutalik Z Kutalik Zoltán Z Institute of Social and Preventive Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Lee SH Lee S Hong 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.
Ripke S Ripke Stephan 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.
Steinberg S Steinberg Stacy S deCODE Genetics, Reykjavik, Iceland.
Teumer A Teumer Alexander A Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
Viktorin A Viktorin Alexander A Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Wray NR Wray Naomi R NR Queensland Brain Institute, The University of Queensland, Brisbane, Queensland.
Arolt V Arolt Volker V Department of Psychiatry and Psychotherapy, University of Muenster, Muenster, Germany.
Baune BT Baune Bernard T BT Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, Australia.
Boomsma DI Boomsma Dorret I DI Department of Biological Psychology, EMGO Institute for Health and Care Research and Neuroscience Campus Amsterdam, Vrije Universiteit, Amsterdam, The Netherlands.
Børglum AD Børglum Anders D 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.
Byrne EM Byrne Enda M EM Queensland Brain Institute, The University of Queensland, Brisbane, Queensland.
Castelao E Castelao Enrique E Department of Psychiatry, Lausanne University Hospital, Lausanne, Switzerland.
Craddock N Craddock Nick N MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, United Kingdom.
Craig IW Craig Ian W IW Institute of Psychiatry, Psychology, and Neuroscience, King׳s College London, London.
Dannlowski U Dannlowski Udo U Department of Psychiatry and Psychotherapy, University of Muenster, Muenster, Germany; Department of Psychiatry, University of Marburg, Marburg, Germany.
Deary IJ Deary Ian J IJ Centre for Cognitive Ageing and Cognitive Epidemiology, Edinburgh, United Kingdom; Department of Psychology, University of Edinburgh, Edinburgh, United Kingdom.
Degenhardt F Degenhardt Franziska F Institute of Human Genetics; Bonn, Germany; Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany.
Forstner AJ Forstner Andreas J AJ Institute of Human Genetics; Bonn, Germany; Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany.
Gordon SD Gordon Scott D SD QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Grabe HJ Grabe Hans J HJ Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
Grove J Grove Jakob 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.
Hamilton SP Hamilton Steven P SP Department of Psychiatry, Kaiser Permanente San Francisco Medical Center, San Francisco, California.
Hayward C Hayward Caroline C Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
Heath AC Heath Andrew C AC Department of Psychiatry, Washington University St. Louis, St. Louis, Missouri.
Hocking LJ Hocking Lynne J LJ Division of Applied Health Sciences, University of Aberdeen, Aberdeen, United Kingdom.
Homuth G Homuth Georg G Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Greifswald.
Hottenga JJ Hottenga Jouke J JJ Department of Biological Psychology, EMGO Institute for Health and Care Research and Neuroscience Campus Amsterdam, Vrije Universiteit, Amsterdam, The Netherlands.
Kloiber S Kloiber Stefan S Max Planck Institute of Psychiatry, Munich, Germany.
Krogh J Krogh Jesper J Mental Health Center Copenhagen, Mental Health Services in Capital Region, University of Copenhagen, Copenhagen, Denmark.
Landén M Landén Mikael M Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.
Lang M Lang Maren M Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
Levinson DF Levinson Douglas F DF Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California.
Lichtenstein P Lichtenstein Paul P Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Lucae S Lucae Susanne S Max Planck Institute of Psychiatry, Munich, Germany.
MacIntyre DJ MacIntyre Donald J DJ Division of Psychiatry, University of Edinburgh, Edinburgh, United Kingdom.
Madden P Madden Pamela P Department of Psychiatry, Washington University St. Louis, St. Louis, Missouri.
Magnusson PK Magnusson Patrik K E PK Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Martin NG Martin Nicholas G NG QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
McIntosh AM McIntosh Andrew M AM Division of Psychiatry, University of Edinburgh, Edinburgh, United Kingdom; Centre for Cognitive Ageing and Cognitive Epidemiology, Edinburgh, United Kingdom.
Middeldorp CM Middeldorp Christel M CM Department of Biological Psychology, EMGO Institute for Health and Care Research and Neuroscience Campus Amsterdam, Vrije Universiteit, Amsterdam, The Netherlands.
Milaneschi Y Milaneschi Yuri Y Department of Psychiatry, EMGO Institute for Health and Care Research and Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
Montgomery GW Montgomery Grant W GW QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Mors O Mors Ole O Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus University, Aarhus, Denmark; Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark.
Müller-Myhsok B Müller-Myhsok Bertram 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.
Nyholt DR Nyholt Dale R DR Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.
Oskarsson H Oskarsson Hogni H Therapeia, Reykjavik, Iceland.
Owen MJ Owen Michael J MJ MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, United Kingdom.
Padmanabhan S Padmanabhan Sandosh S Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom.
Penninx BW Penninx Brenda W J H BW Department of Psychiatry, EMGO Institute for Health and Care Research and Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
Pergadia ML Pergadia Michele L ML Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, Florida.
Porteous DJ Porteous David J DJ Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.
Potash JB Potash James B JB Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa.
Preisig M Preisig Martin M Department of Psychiatry, Lausanne University Hospital, Lausanne, Switzerland.
Rivera M Rivera Margarita 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.
Shi J Shi Jianxin J Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
Shyn SI Shyn Stanley I SI Department of Psychiatry, Group Health, Seattle, Washington.
Sigurdsson E Sigurdsson Engilbert E University of Iceland; Department of Psychiatry, Landspitali University Hospital, Reykjavik, Iceland.
Smit JH Smit Johannes H JH Department of Psychiatry, EMGO Institute for Health and Care Research and Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
Smith BH Smith Blair H BH Division of Population Health Sciences, University of Dundee, Dundee, United Kingdom.
Stefansson H Stefansson Hreinn H deCODE Genetics, Reykjavik, Iceland.
Stefansson K Stefansson Kari K deCODE Genetics, Reykjavik, Iceland.
Strohmaier J Strohmaier Jana J Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
Sullivan PF Sullivan Patrick F 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.
Thomson P Thomson Pippa 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.
Thorgeirsson TE Thorgeirsson Thorgeir E TE deCODE Genetics, Reykjavik, Iceland.
Van der Auwera S Van der Auwera Sandra S Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
Weissman MM Weissman Myrna M 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.
CONVERGE Consortium, CARDIoGRAM Consortium, GERAD1 Consortium
Breen G Breen Gerome G Institute of Psychiatry, Psychology, and Neuroscience, King׳s College London, London.
Lewis CM Lewis Cathryn M CM Institute of Psychiatry, Psychology, and Neuroscience, King׳s College London, London. Electronic address: cathryn.lewis@kcl.ac.uk.
INVESTIGATORS
JOURNAL
VOLUME:
ISSUE:
TITLE: Biological psychiatry
ISOABBREVIATION: Biol. Psychiatry
YEAR: 2016
MONTH: May
DAY: 24
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1873-2402
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Biol Psychiatry
COUNTRY: United States
ISSNLINKING: 0006-3223
NLMUNIQUEID: 0213264
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
JOURNAL ARTICLE
COMMENTS AND CORRECTIONS
GRANTS
GENERAL NOTE
KEYWORDS
KEYWORD
Age at onset
GWAS
Heterogeneity
Major depressive disorder
Polygenic scoring
Stratification
MESH HEADINGS
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's