Genetic Epidemiology, Translational Neurogenomics, Psychiatric 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
28350396
TITLE
Genetic effects influencing risk for major depressive disorder in China and Europe.
ABSTRACT
Major depressive disorder (MDD) is a common, complex psychiatric disorder and a leading cause of disability worldwide. Despite twin studies indicating its modest heritability (~30-40%), extensive heterogeneity and a complex genetic architecture have complicated efforts to detect associated genetic risk variants. We combined single-nucleotide polymorphism (SNP) summary statistics from the CONVERGE and PGC studies of MDD, representing 10 502 Chinese (5282 cases and 5220 controls) and 18 663 European (9447 cases and 9215 controls) subjects. We determined the fraction of SNPs displaying consistent directions of effect, assessed the significance of polygenic risk scores and estimated the genetic correlation of MDD across ancestries. Subsequent trans-ancestry meta-analyses combined SNP-level evidence of association. Sign tests and polygenic score profiling weakly support an overlap of SNP effects between East Asian and European populations. We estimated the trans-ancestry genetic correlation of lifetime MDD as 0.33; female-only and recurrent MDD yielded estimates of 0.40 and 0.41, respectively. Common variants downstream of GPHN achieved genome-wide significance by Bayesian trans-ancestry meta-analysis (rs9323497; log10 Bayes Factor=8.08) but failed to replicate in an independent European sample (P=0.911). Gene-set enrichment analyses indicate enrichment of genes involved in neuronal development and axonal trafficking. We successfully demonstrate a partially shared polygenic basis of MDD in East Asian and European populations. Taken together, these findings support a complex etiology for MDD and possible population differences in predisposing genetic factors, with important implications for future genetic studies.
DATE PUBLISHED
2017 Mar 28
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2016/11/19
accepted 2016/11/27
entrez 2017/03/29 06:00
pubmed 2017/03/30 06:00
medline 2017/03/30 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Bigdeli TB Bigdeli T B TB Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
Ripke S Ripke S S Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
Peterson RE Peterson R E RE Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
Trzaskowski M Trzaskowski M M Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.
Bacanu SA Bacanu S-A SA Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
Abdellaoui A Abdellaoui A A Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Andlauer TF Andlauer T F M TF Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
Beekman AT Beekman A T F AT Department of Psychiatry, VU University Medical Center and GGZ inGeest, Amsterdam, The Netherlands.
Berger K Berger K K Institute of Epidemiology and Social Medicine, University of Muenster, Münster, Germany.
Blackwood DH Blackwood D H R DH Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
Boomsma DI Boomsma D I DI Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Breen G Breen G G King's College London, MRC Social Genetic and Developmental Psychiatry Centre, London, UK.
Buttenschøn HN Buttenschøn H N HN Department of Clinical Medicine, Translational Neuropsychiatry Unit, Aarhus University, Aarhus, Denmark.
Byrne EM Byrne E M EM Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.
Cichon S Cichon S S Institute of Human Genetics, University of Bonn, Bonn, Germany.
Clarke TK Clarke T-K TK Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
Couvy-Duchesne B Couvy-Duchesne B B Centre for Advanced Imaging, University of Queensland, Brisbane, QLD, Australia.
Craddock N Craddock N N Department of Psychological Medicine, Cardiff University, Cardiff, UK.
de Geus EJ de Geus E J C EJ EMGO+ Institute, VU University Medical Center, Amsterdam, The Netherlands.
Degenhardt F Degenhardt F F Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany.
Dunn EC Dunn E C EC Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
Edwards AC Edwards A C AC Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
Fanous AH Fanous A H AH Department of Psychiatry and Behavioral Sciences, State University of New York Downstate Medical Center, Brooklyn, NY, USA.
Forstner AJ Forstner A J AJ Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany.
Frank J Frank J J Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany.
Gill M Gill M M Department of Psychiatry, Trinity College Dublin, Dublin, Ireland.
Gordon SD Gordon S D SD Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Grabe HJ Grabe H J HJ Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
Hamilton SP Hamilton S P SP Department of Psychiatry, Kaiser-Permanente Northern California, San Fransisco, CA, USA.
Hardiman O Hardiman O O Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland.
Hayward C Hayward C C Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Heath AC Heath A C AC Department of Psychiatry, Washington University in Saint Louis School of Medicine, St Louis, MO, USA.
Henders AK Henders A K AK Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.
Herms S Herms S S Division of Medical Genetics, Department of Biomedicine, University of Basel, Basel, Switzerland.
Hickie IB Hickie I B IB Brain and Mind Research Institute, University of Sydney, Sydney, NSW, Australia.
Hoffmann P Hoffmann P P Human Genomics Research Group, Department of Biomedicine, University of Basel, Basel, Switzerland.
Homuth G Homuth G G Department of Functional Genomics, Interfaculty Institute for Genetics and Functional Genomics, University Medicine and Ernst Moritz Arndt University Greifswald, Greifswald, Germany.
Hottenga JJ Hottenga J-J JJ Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Ising M Ising M M Max Planck Institute of Psychiatry, Munich, Germany.
Jansen R Jansen R R Department of Psychiatry, VU University Medical Center and GGZ inGeest, Amsterdam, The Netherlands.
Kloiber S Kloiber S S Max Planck Institute of Psychiatry, Munich, Germany.
Knowles JA Knowles J A JA Department of Psychiatry and The Behavioral Sciences, University of Southern California, Los Angeles, CA, USA.
Lang M Lang M M Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany.
Li QS Li Q S QS Neuroscience Therapeutic Area, Janssen Research and Development, LLC, Titusville, NJ, USA.
Lucae S Lucae S S Max Planck Institute of Psychiatry, Munich, Germany.
MacIntyre DJ MacIntyre D J DJ Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
Madden PA Madden P A F PA Department of Psychiatry, Washington University in Saint Louis School of Medicine, St Louis, MO, USA.
Martin NG Martin N G NG School of Psychology, University of Queensland, Brisbane, QLD, Australia.
McGrath PJ McGrath P J PJ Department of Psychiatry, New York State Psychiatric Institute, Columbia University College of Physicians and Surgeons, New York, NY, USA.
McGuffin P McGuffin P P King's College London, MRC Social Genetic and Developmental Psychiatry Centre, London, UK.
McIntosh AM McIntosh A M AM Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
Medland SE Medland S E SE Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Mehta D Mehta D D Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.
Middeldorp CM Middeldorp C M CM Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Milaneschi Y Milaneschi Y Y Department of Psychiatry, VU University Medical Center and GGZ inGeest, Amsterdam, The Netherlands.
Montgomery GW Montgomery G W GW Institute for Molecular Biology, University of Queensland, Brisbane, QLD, Australia.
Mors O Mors O O Psychosis Research Unit, Aarhus University Hospital, Risskov, Denmark.
Müller-Myhsok B Müller-Myhsok B B Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK.
Nauck M Nauck M M Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.
Nyholt DR Nyholt D R DR Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia.
Nöthen MM Nöthen M M MM Department of Genomics, Life and Brain Center, University of Bonn, Bonn, Germany.
Owen MJ Owen M J MJ MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University School of Medicine, Cardiff, UK.
Penninx BW Penninx B W J H BW Department of Psychiatry, VU University Medical Center and GGZ inGeest, Amsterdam, The Netherlands.
Pergadia ML Pergadia M L ML Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL, USA.
Perlis RH Perlis R H RH Department of Psychiatry, Massachusetts General Hospital, Boston, MA, USA.
Peyrot WJ Peyrot W J WJ Department of Psychiatry, VU University Medical Center and GGZ inGeest, Amsterdam, The Netherlands.
Porteous DJ Porteous D J DJ Medical Genetics Section, CGEM, IGMM, University of Edinburgh, Edinburgh, UK.
Potash JB Potash J B JB Department of Psychiatry, University of Iowa, Iowa, IA, USA.
Rice JP Rice J P JP Department of Psychiatry, Washington University in Saint Louis, St Louis, MO, USA.
Rietschel M Rietschel M M Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany.
Riley BP Riley B P BP Department of Human and Molecular Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
Rivera M Rivera M M King's College London, MRC Social Genetic and Developmental Psychiatry Centre, London, UK.
Schoevers R Schoevers R R Department of Psychiatry, University of Groningen, University of Medical Center Groningen, Groningen, The Netherlands.
Schulze TG Schulze T G TG Human Genetics Branch, NIMH Division of Intramural Research Programs, Bethesda, MD, USA.
Shi J Shi J J Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Shyn SI Shyn S I SI Division of Psychiatry, Group Health, Seattle, WA, USA.
Smit JH Smit J H JH Department of Psychiatry, VU University Medical Center and GGZ inGeest, Amsterdam, The Netherlands.
Smoller JW Smoller J W JW Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
Streit F Streit F F Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany.
Strohmaier J Strohmaier J J Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany.
Teumer A Teumer A A Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
Treutlein J Treutlein J J Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany.
Van der Auwera S Van der Auwera S S Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
van Grootheest G van Grootheest G G Department of Psychiatry, VU University Medical Center and GGZ inGeest, Amsterdam, The Netherlands.
van Hemert AM van Hemert A M AM Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands.
Völzke H Völzke H H Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
Webb BT Webb B T BT Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
Weissman MM Weissman M M MM Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, USA.
Wellmann J Wellmann J J Institute of Epidemiology and Social Medicine, University of Muenster, Münster, Germany.
Willemsen G Willemsen G G Department of Biological Psychology, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Witt SH Witt S H SH Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany.
Levinson DF Levinson D F DF Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
Lewis CM Lewis C M CM King's College London, Department of Medical and Molecular Genetics, London, UK.
Wray NR Wray N R NR Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia.
Flint J Flint J J Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Sullivan PF Sullivan P F PF Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Kendler KS Kendler K S KS Department of Human and Molecular Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
INVESTIGATORS
JOURNAL
VOLUME: 7
ISSUE: 3
TITLE: Translational psychiatry
ISOABBREVIATION: Transl Psychiatry
YEAR: 2017
MONTH: Mar
DAY: 28
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 2158-3188
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Transl Psychiatry
COUNTRY: United States
ISSNLINKING: 2158-3188
NLMUNIQUEID: 101562664
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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