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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28049566
TITLE
An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype.
ABSTRACT
BACKGROUND NlmCategory: BACKGROUND
The genetics of depression has been explored in genome-wide association studies that focused on either major depressive disorder or depressive symptoms with mostly negative findings. A broad depression phenotype including both phenotypes has not been tested previously using a genome-wide association approach. We aimed to identify genetic polymorphisms significantly associated with a broad phenotype from depressive symptoms to major depressive disorder.
METHODS NlmCategory: METHODS
We analyzed two prior studies of 70,017 participants of European ancestry from general and clinical populations in the discovery stage. We performed a replication meta-analysis of 28,328 participants. Single nucleotide polymorphism (SNP)-based heritability and genetic correlations were calculated using linkage disequilibrium score regression. Discovery and replication analyses were performed using a p-value-based meta-analysis. Lifetime major depressive disorder and depressive symptom scores were used as the outcome measures.
RESULTS NlmCategory: RESULTS
The SNP-based heritability of major depressive disorder was 0.21 (SE = 0.02), the SNP-based heritability of depressive symptoms was 0.04 (SE = 0.01), and their genetic correlation was 1.001 (SE = 0.2). We found one genome-wide significant locus related to the broad depression phenotype (rs9825823, chromosome 3: 61,082,153, p = 8.2 × 10(-9)) located in an intron of the FHIT gene. We replicated this SNP in independent samples (p = .02) and the overall meta-analysis of the discovery and replication cohorts (1.0 × 10(-9)).
CONCLUSIONS NlmCategory: CONCLUSIONS
This large study identified a new locus for depression. Our results support a continuum between depressive symptoms and major depressive disorder. A phenotypically more inclusive approach may help to achieve the large sample sizes needed to detect susceptibility loci for depression.
Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
DATE PUBLISHED
2016 Dec 08
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2016/08/03
revised 2016/11/11
accepted 2016/11/22
entrez 2017/01/05 06:00
pubmed 2017/01/05 06:00
medline 2017/01/05 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Direk N Direk Nese N Department of Epidemiology, Erasmus University Medical Center, Rotterdam; Department of Psychiatry, Dokuz Eylul University, Izmir, Turkey.
Williams S Williams Stephanie S Department of Genetics, Genomic Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Smith JA Smith Jennifer A JA Department of Epidemiology, University of Michigan, Ann Arbor, Michigan.
Ripke S Ripke Stephan S Stanley Center for Psychiatric Research, The Broad Institute of Harvard and MIT, Cambridge; Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston; Department of Psychiatry and Psychotherapy, Charité, Campus Mitte, Berlin.
Air T Air Tracy T Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, South Australia.
Amare AT Amare Azmeraw T AT Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen; Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, South Australia.
Amin N Amin Najaf N Genetic Epidemiology Unit, Erasmus University Medical Center, Rotterdam.
Baune BT Baune Bernhard T BT Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, South Australia.
Bennett DA Bennett David A DA Rush Alzheimer's Disease Center & Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois.
Blackwood DH Blackwood Douglas H R DH Division of Psychiatry, University of Edinburgh, Edinburgh.
Boomsma D Boomsma Dorret D Department of Biological Psychology, VU University, Amsterdam, The Netherlands.
Breen G Breen Gerome G MRC Social, Genetic & Developmental Psychiatry Centre Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London.
Buttenschøn HN Buttenschøn Henriette N HN Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus.
Byrne EM Byrne Enda M EM Queensland Brain Institute, University of Queensland, St. Lucia, Queensland.
Børglum AD Børglum Anders D AD Department of Biomedicine and Centre for Integrative Sequencing, Aarhus University, Aarhus; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus.
Castelao E Castelao Enrique E Department of Psychiatry, Lausanne University Hospital, Lausanne.
Cichon S Cichon Sven S Institute of Human Genetics, University of Bonn, Bonn; Department of Genomics, Life & Brain Center, Bonn; Institute of Neuroscience and Medicine, Research Centre Jülich, Jülich; Division of Medical Genetics, Department of Biomedicine, University of Basel, Basel, Switzerland.
Clarke TK Clarke Toni-Kim TK Division of Psychiatry, University of Edinburgh, Edinburgh.
Cornelis MC Cornelis Marilyn C MC Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Dannlowski U Dannlowski Udo U Department of Psychiatry and Psychotherapy, University of Münster, Münster.
De Jager PL De Jager Philip L PL Program in Medical and Population Genetics, The Broad Institute of Harvard and MIT, Cambridge; Department of Neurology, Program in Translational NeuroPsychiatric Genomics, Brigham and Women's Hospital, Harvard Medical School, Boston; Department of Neurology, Harvard Medical School, Boston.
Demirkan A Demirkan Ayse A Genetic Epidemiology Unit, Erasmus University Medical Center, Rotterdam.
Domenici E Domenici Enrico E Roche Pharmaceutical Research and Early Development, Neuroscience, Ophthalmology and Rare Diseases Discovery & Translational Medicine Area, Roche Innovation Center Basel, F Hoffman-La Roche Ltd., Basel, Switzerland; Centre for Integrative Biology, University of Trento, Trento, Italy.
van Duijn CM van Duijn Cornelia M CM Genetic Epidemiology Unit, Erasmus University Medical Center, Rotterdam.
Dunn EC Dunn Erin C EC Stanley Center for Psychiatric Research, The Broad Institute of Harvard and MIT, Cambridge; Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston; Department of Psychiatry, Harvard Medical School, Boston.
Eriksson JG Eriksson Johan G JG National Institute for Health and Welfare, Department of Chronic Disease Prevention, Helsinki; Department of General Practice and Primary Health Care, University of Helsinki, Helsinki; Unit of General Practice, Helsinki University Central Hospital, Helsinki; Folkhalsan Research Centre, Helsinki; Vasa Central Hospital, Vasa, Finland.
Esko T Esko Tonu T Program in Medical and Populational Genetics, The Broad Institute of Harvard and MIT, Cambridge; Division of Endocrinology, Boston Children's Hospital, Cambridge; Department of Genetics, Harvard Medical School, Boston; Estonian Genome Center, University of Tartu, Tartu, Estonia.
Faul JD Faul Jessica D JD Institute for Social Research, University of Michigan, Ann Arbor, Michigan.
Ferrucci L Ferrucci Luigi L Translational Gerontology Branch, National Institute on Aging, Baltimore, Maryland.
Fornage M Fornage Myriam M Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas.
de Geus E de Geus Eco E Department of Biological Psychology, VU University, Amsterdam, The Netherlands.
Gill M Gill Michael M Department of Psychiatry, Trinity Centre for Health Science, Dublin, Ireland.
Gordon SD Gordon Scott D SD QIMR Berghofer Medical Research Institute, Brisbane.
Grabe HJ Grabe Hans Jörgen HJ Department of Psychiatry and Psychotherapy, Helios Hospital Stralsund, Munich; Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Munich; German Center for Neurodegenerative Diseases, Site Rostock/Greifswald, Munich.
van Grootheest G van Grootheest Gerard G Department of Psychiatry, Neuroscience Campus Amsterdam and EMGO Institute of Health and Care Research, VU University, Amsterdam, The Netherlands.
Hamilton SP Hamilton Steven P SP Department of Psychiatry, Kaiser Permanente San Francisco Medical Center, San Francisco.
Hartman CA Hartman Catharina A CA Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen.
Heath AC Heath Andrew C AC Department of Psychiatry, Washington University, St. Louis, Missouri.
Hek K Hek Karin K Department of Epidemiology, Erasmus University Medical Center, Rotterdam; Department of Psychiatry, Erasmus University Medical Center, Rotterdam.
Hofman A Hofman Albert A Department of Epidemiology, Erasmus University Medical Center, Rotterdam.
Homuth G Homuth Georg G Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Munich.
Horn C Horn Carsten C Roche Pharmaceutical Research and Early Development, Neuroscience, Ophthalmology and Rare Diseases Discovery & Translational Medicine Area, Roche Innovation Center Basel, F Hoffman-La Roche Ltd., Basel, Switzerland.
Jan Hottenga J Jan Hottenga Jouke J Department of Biological Psychology, VU University, Amsterdam, The Netherlands.
Kardia SL Kardia Sharon L R SL Department of Epidemiology, University of Michigan, Ann Arbor, Michigan.
Kloiber S Kloiber Stefan S Max Planck Institute of Psychiatry, Munich.
Koenen K Koenen Karestan K Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York.
Kutalik Z Kutalik Zoltán Z Institute of Social and Preventive Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne.
Ladwig KH Ladwig Karl-Heinz KH Department of Psychosomatic Medicine and Psychotherapy, Klinikum rechts der Isar, Technische Universität München, Munich; Institute of Epidemiology II, Mental Health Research Unit, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg.
Lahti J Lahti Jari J Folkhalsan Research Centre, Helsinki; Institute of Behavioural Sciences, University of Helsinki, Helsinki.
Levinson DF Levinson Douglas F DF Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California.
Lewis CM Lewis Cathryn M CM MRC Social, Genetic & Developmental Psychiatry Centre Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London.
Lewis G Lewis Glyn G Division of Psychiatry, University College London, London.
Li QS Li Qingqin S QS Janssen Research & Development LLC, New Brunswick, New Jersey.
Llewellyn DJ Llewellyn David J DJ University of Exeter Medical School, Exeter.
Lucae S Lucae Susanne S Max Planck Institute of Psychiatry, Munich.
Lunetta KL Lunetta Kathryn L KL Department of Biostatistics, Boston University School of Public Health, Framingham, Massachusetts; Boston University and National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts.
MacIntyre DJ MacIntyre Donald J DJ Division of Psychiatry, University of Edinburgh, Edinburgh.
Madden P Madden Pamela P Department of Psychiatry, Washington University, St. Louis, Missouri.
Martin NG Martin Nicholas G NG QIMR Berghofer Medical Research Institute, Brisbane.
McIntosh AM McIntosh Andrew M AM Division of Psychiatry, University of Edinburgh, Edinburgh.
Metspalu A Metspalu Andres A Estonian Genome Center, University of Tartu, Tartu, Estonia; Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
Milaneschi Y Milaneschi Yuri Y Department of Psychiatry, Neuroscience Campus Amsterdam and EMGO Institute of Health and Care Research, VU University, Amsterdam, The Netherlands.
Montgomery GW Montgomery Grant W GW QIMR Berghofer Medical Research Institute, Brisbane.
Mors O Mors Ole O The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus; Research Department P, Aarhus University Hospital, Risskov, Denmark.
Mosley TH Jr Mosley Thomas H TH Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi.
Murabito JM Murabito Joanne M JM Department of Medicine, Section of General Internal Medicine, Boston University School of Medicine, Boston; Boston University and National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts.
Müller-Myhsok B Müller-Myhsok Bertram B Max Planck Institute of Psychiatry, Munich; Munich Cluster for Systems Neurology, Munich; University of Liverpool, Institute of Translational Medicine, Liverpool.
Nöthen MM Nöthen Markus M MM Institute of Human Genetics, University of Bonn, Bonn; Department of Genomics, Life & Brain Center, Bonn.
Nyholt DR Nyholt Dale R DR QIMR Berghofer Medical Research Institute, Brisbane; Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland.
O'Donovan MC O'Donovan Michael C MC MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, United Kingdom.
Penninx BW Penninx Brenda W BW Department of Psychiatry, Neuroscience Campus Amsterdam and EMGO Institute of Health and Care Research, VU University, Amsterdam, The Netherlands.
Pergadia ML Pergadia Michele L ML Department of Psychiatry, Washington University, St. Louis, Missouri; Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, Florida.
Perlis R Perlis Roy R Center for Experimental Drugs and Diagnostics, Massachusetts General Hospital and Harvard Medical School, Boston.
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.
Purcell SM Purcell Shaun M SM Division of Psychiatric Genomics, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York.
Quiroz JA Quiroz Jorge A JA Solid GT, Boston; Roche Pharmaceutical Research and Early Development, Neuroscience, Ophthalmology and Rare Diseases Discovery & Translational Medicine Area, Roche Innovation Center Basel, F Hoffman-La Roche Ltd., Basel, Switzerland.
Räikkönen K Räikkönen Katri K Institute of Behavioural Sciences, University of Helsinki, Helsinki.
Rice JP Rice John P JP Department of Psychiatry, Washington University, St. Louis, Missouri.
Rietschel M Rietschel Marcella M Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim.
Rivera M Rivera Margarita M MRC Social, Genetic & Developmental Psychiatry Centre Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London; CIBERSAM-Universidad de Granada, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain; Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain.
Schulze TG Schulze Thomas G TG Institute of Psychiatric Phenomics and Genomics, Ludwig-Maximilians-University, Munich; Department of Psychiatry and Psychotherapy, University of Göttingen, Göttingen, Germany.
Shi J Shi Jianxin J Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
Shyn S Shyn Stanley S Group Health, Seattle, Washington.
Sinnamon GC Sinnamon Grant C GC Department of Psychiatry and Psychiatric Neuroscience, School of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia.
Smit JH Smit Johannes H JH Department of Psychiatry, Neuroscience Campus Amsterdam and EMGO Institute of Health and Care Research, VU University, Amsterdam, The Netherlands.
Smoller JW Smoller Jordan W JW Stanley Center for Psychiatric Research, The Broad Institute of Harvard and MIT, Cambridge; Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston; Department of Psychiatry, Harvard Medical School, Boston.
Snieder H Snieder Harold H Unit of Genetic Epidemiology & Bioinformatics, University Medical Center Groningen, University of Groningen, Groningen.
Tanaka T Tanaka Toshiko T Translational Gerontology Branch, National Institute on Aging, Baltimore, Maryland.
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.
Teumer A Teumer Alexander A Institute for Community Medicine, University Medicine Greifswald, Greifswald, Munich.
Uher R Uher Rudolf R MRC Social, Genetic & Developmental Psychiatry Centre Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London; Dalhousie University, Halifax, Nova Scotia, Canada.
Umbricht D Umbricht Daniel D Roche Pharmaceutical Research and Early Development, Neuroscience, Ophthalmology and Rare Diseases Discovery & Translational Medicine Area, Roche Innovation Center Basel, F Hoffman-La Roche Ltd., Basel, Switzerland.
Van der Auwera S Van der Auwera Sandra S Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Munich; German Center for Neurodegenerative Diseases, Site Rostock/Greifswald, Munich.
Ware EB Ware Erin B EB Department of Epidemiology, University of Michigan, Ann Arbor, Michigan; Institute for Social Research, University of Michigan, Ann Arbor, Michigan.
Weir DR Weir David R DR Institute for Social Research, University of Michigan, Ann Arbor, Michigan.
Weissman MM Weissman Myrna M MM College of Physicians and Surgeons, Columbia University and New York State Psychiatric Institute, New York, New York.
Willemsen G Willemsen Gonneke G Department of Biological Psychology, VU University, Amsterdam, The Netherlands.
Yang J Yang Jingyun J Rush Alzheimer's Disease Center & Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois.
Zhao W Zhao Wei W Department of Epidemiology, University of Michigan, Ann Arbor, Michigan.
Tiemeier H Tiemeier Henning H Department of Epidemiology, Erasmus University Medical Center, Rotterdam; Department of Psychiatry, Erasmus University Medical Center, Rotterdam. Electronic address: h.tiemeier@erasmusmc.nl.
Sullivan PF Sullivan Patrick F PF Department of Psychiatry, Genomic Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Center for Psychiatric Genomics, Genomic Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Sweden.
INVESTIGATORS
JOURNAL
VOLUME:
ISSUE:
TITLE: Biological psychiatry
ISOABBREVIATION: Biol. Psychiatry
YEAR: 2016
MONTH: Dec
DAY: 08
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
GRANTID AGENCY COUNTRY
R01 MH077139 NIMH NIH HHS United States
GENERAL NOTE
KEYWORDS
KEYWORD
CHARGE consortium
Depressive symptoms
FHIT gene
Genome-wide association study
Major depressive disorder
Psychiatric Genomics Consortium
MESH HEADINGS
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
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