Meta-Analysis

. 2017 Sep 1;82(5):322-329.

doi: 10.1016/j.biopsych.2016.11.013. Epub 2016 Dec 8.

An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype

Nese Direk¹, Stephanie Williams², Jennifer A Smith³, Stephan Ripke⁴, Tracy Air⁵, Azmeraw T Amare⁶, Najaf Amin⁷, Bernhard T Baune⁵, David A Bennett⁸, Douglas H R Blackwood⁹, Dorret Boomsma¹⁰, Gerome Breen¹¹, Henriette N Buttenschøn¹², Enda M Byrne¹³, Anders D Børglum¹⁴, Enrique Castelao¹⁵, Sven Cichon¹⁶, Toni-Kim Clarke⁹, Marilyn C Cornelis¹⁷, Udo Dannlowski¹⁸, Philip L De Jager¹⁹, Ayse Demirkan⁷, Enrico Domenici²⁰, Cornelia M van Duijn⁷, Erin C Dunn²¹, Johan G Eriksson²², Tonu Esko²³, Jessica D Faul²⁴, Luigi Ferrucci²⁵, Myriam Fornage²⁶, Eco de Geus¹⁰, Michael Gill²⁷, Scott D Gordon²⁸, Hans Jörgen Grabe²⁹, Gerard van Grootheest³⁰, Steven P Hamilton³¹, Catharina A Hartman³², Andrew C Heath³³, Karin Hek³⁴, Albert Hofman³⁵, Georg Homuth³⁶, Carsten Horn³⁷, Jouke Jan Hottenga¹⁰, Sharon L R Kardia³, Stefan Kloiber³⁸, Karestan Koenen³⁹, Zoltán Kutalik⁴⁰, Karl-Heinz Ladwig⁴¹, Jari Lahti⁴², Douglas F Levinson⁴³, Cathryn M Lewis¹¹, Glyn Lewis⁴⁴, Qingqin S Li⁴⁵, David J Llewellyn⁴⁶, Susanne Lucae³⁸, Kathryn L Lunetta⁴⁷, Donald J MacIntyre⁹, Pamela Madden³³, Nicholas G Martin²⁸, Andrew M McIntosh⁹, Andres Metspalu⁴⁸, Yuri Milaneschi³⁰, Grant W Montgomery²⁸, Ole Mors⁴⁹, Thomas H Mosley Jr⁵⁰, Joanne M Murabito⁵¹, Bertram Müller-Myhsok⁵², Markus M Nöthen⁵³, Dale R Nyholt⁵⁴, Michael C O'Donovan⁵⁵, Brenda W Penninx³⁰, Michele L Pergadia⁵⁶, Roy Perlis⁵⁷, James B Potash⁵⁸, Martin Preisig¹⁵, Shaun M Purcell⁵⁹, Jorge A Quiroz⁶⁰, Katri Räikkönen⁶¹, John P Rice³³, Marcella Rietschel⁶², Margarita Rivera⁶³, Thomas G Schulze⁶⁴, Jianxin Shi⁶⁵, Stanley Shyn⁶⁶, Grant C Sinnamon⁶⁷, Johannes H Smit³⁰, Jordan W Smoller²¹, Harold Snieder⁶⁸, Toshiko Tanaka²⁵, Katherine E Tansey⁵⁵, Alexander Teumer⁶⁹, Rudolf Uher⁷⁰, Daniel Umbricht³⁷, Sandra Van der Auwera⁷¹, Erin B Ware⁷², David R Weir²⁴, Myrna M Weissman⁷³, Gonneke Willemsen¹⁰, Jingyun Yang⁸, Wei Zhao³, Henning Tiemeier⁷⁴, Patrick F Sullivan⁷⁵

Affiliations

¹ Department of Epidemiology, Erasmus University Medical Center, Rotterdam; Department of Psychiatry, Dokuz Eylul University, Izmir, Turkey.
² Department of Genetics, Genomic Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
³ Department of Epidemiology, University of Michigan, Ann Arbor, Michigan.
⁴ 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.
⁵ Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, South Australia.
⁶ Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen; Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, South Australia.
⁷ Genetic Epidemiology Unit, Erasmus University Medical Center, Rotterdam.
⁸ Rush Alzheimer's Disease Center & Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois.
⁹ Division of Psychiatry, University of Edinburgh, Edinburgh.
¹⁰ Department of Biological Psychology, VU University, Amsterdam, The Netherlands.
¹¹ MRC Social, Genetic & Developmental Psychiatry Centre Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London.
¹² Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus.
¹³ Queensland Brain Institute, University of Queensland, St. Lucia, Queensland.
¹⁴ Department of Biomedicine and Centre for Integrative Sequencing, Aarhus University, Aarhus; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus.
¹⁵ Department of Psychiatry, Lausanne University Hospital, Lausanne.
¹⁶ 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.
¹⁷ Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
¹⁸ Department of Psychiatry and Psychotherapy, University of Münster, Münster.
¹⁹ 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.
²⁰ 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.
²¹ 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.
²² 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.
²³ 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.
²⁴ Institute for Social Research, University of Michigan, Ann Arbor, Michigan.
²⁵ Translational Gerontology Branch, National Institute on Aging, Baltimore, Maryland.
²⁶ Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas.
²⁷ Department of Psychiatry, Trinity Centre for Health Science, Dublin, Ireland.
²⁸ QIMR Berghofer Medical Research Institute, Brisbane.
²⁹ 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.
³⁰ Department of Psychiatry, Neuroscience Campus Amsterdam and EMGO Institute of Health and Care Research, VU University, Amsterdam, The Netherlands.
³¹ Department of Psychiatry, Kaiser Permanente San Francisco Medical Center, San Francisco.
³² Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen.
³³ Department of Psychiatry, Washington University, St. Louis, Missouri.
³⁴ Department of Epidemiology, Erasmus University Medical Center, Rotterdam; Department of Psychiatry, Erasmus University Medical Center, Rotterdam.
³⁵ Department of Epidemiology, Erasmus University Medical Center, Rotterdam.
³⁶ Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Munich.
³⁷ 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.
³⁸ Max Planck Institute of Psychiatry, Munich.
³⁹ Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York.
⁴⁰ Institute of Social and Preventive Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne.
⁴¹ 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.
⁴² Folkhalsan Research Centre, Helsinki; Institute of Behavioural Sciences, University of Helsinki, Helsinki.
⁴³ Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California.
⁴⁴ Division of Psychiatry, University College London, London.
⁴⁵ Janssen Research & Development LLC, New Brunswick, New Jersey.
⁴⁶ University of Exeter Medical School, Exeter.
⁴⁷ 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.
⁴⁸ Estonian Genome Center, University of Tartu, Tartu, Estonia; Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
⁴⁹ The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus; Research Department P, Aarhus University Hospital, Risskov, Denmark.
⁵⁰ Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi.
⁵¹ 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.
⁵² Max Planck Institute of Psychiatry, Munich; Munich Cluster for Systems Neurology, Munich; University of Liverpool, Institute of Translational Medicine, Liverpool.
⁵³ Institute of Human Genetics, University of Bonn, Bonn; Department of Genomics, Life & Brain Center, Bonn.
⁵⁴ QIMR Berghofer Medical Research Institute, Brisbane; Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland.
⁵⁵ MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, United Kingdom.
⁵⁶ Department of Psychiatry, Washington University, St. Louis, Missouri; Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, Florida.
⁵⁷ Center for Experimental Drugs and Diagnostics, Massachusetts General Hospital and Harvard Medical School, Boston.
⁵⁸ Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa.
⁵⁹ Division of Psychiatric Genomics, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York.
⁶⁰ 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.
⁶¹ Institute of Behavioural Sciences, University of Helsinki, Helsinki.
⁶² Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim.
⁶³ 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.
⁶⁴ Institute of Psychiatric Phenomics and Genomics, Ludwig-Maximilians-University, Munich; Department of Psychiatry and Psychotherapy, University of Göttingen, Göttingen, Germany.
⁶⁵ Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
⁶⁶ Group Health, Seattle, Washington.
⁶⁷ Department of Psychiatry and Psychiatric Neuroscience, School of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia.
⁶⁸ Unit of Genetic Epidemiology & Bioinformatics, University Medical Center Groningen, University of Groningen, Groningen.
⁶⁹ Institute for Community Medicine, University Medicine Greifswald, Greifswald, Munich.
⁷⁰ MRC Social, Genetic & Developmental Psychiatry Centre Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London; Dalhousie University, Halifax, Nova Scotia, Canada.
⁷¹ Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Munich; German Center for Neurodegenerative Diseases, Site Rostock/Greifswald, Munich.
⁷² Department of Epidemiology, University of Michigan, Ann Arbor, Michigan; Institute for Social Research, University of Michigan, Ann Arbor, Michigan.
⁷³ College of Physicians and Surgeons, Columbia University and New York State Psychiatric Institute, New York, New York.
⁷⁴ Department of Epidemiology, Erasmus University Medical Center, Rotterdam; Department of Psychiatry, Erasmus University Medical Center, Rotterdam. Electronic address: h.tiemeier@erasmusmc.nl.
⁷⁵ 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.

PMID: 28049566
PMCID: PMC5462867
DOI: 10.1016/j.biopsych.2016.11.013

Meta-Analysis

An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype

Nese Direk et al. Biol Psychiatry. 2017.

. 2017 Sep 1;82(5):322-329.

doi: 10.1016/j.biopsych.2016.11.013. Epub 2016 Dec 8.

Authors

Affiliations

¹ Department of Epidemiology, Erasmus University Medical Center, Rotterdam; Department of Psychiatry, Dokuz Eylul University, Izmir, Turkey.
² Department of Genetics, Genomic Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
³ Department of Epidemiology, University of Michigan, Ann Arbor, Michigan.
⁴ 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.
⁵ Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, South Australia.
⁶ Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen; Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, South Australia.
⁷ Genetic Epidemiology Unit, Erasmus University Medical Center, Rotterdam.
⁸ Rush Alzheimer's Disease Center & Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois.
⁹ Division of Psychiatry, University of Edinburgh, Edinburgh.
¹⁰ Department of Biological Psychology, VU University, Amsterdam, The Netherlands.
¹¹ MRC Social, Genetic & Developmental Psychiatry Centre Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London.
¹² Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus.
¹³ Queensland Brain Institute, University of Queensland, St. Lucia, Queensland.
¹⁴ Department of Biomedicine and Centre for Integrative Sequencing, Aarhus University, Aarhus; The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus.
¹⁵ Department of Psychiatry, Lausanne University Hospital, Lausanne.
¹⁶ 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.
¹⁷ Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
¹⁸ Department of Psychiatry and Psychotherapy, University of Münster, Münster.
¹⁹ 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.
²⁰ 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.
²¹ 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.
²² 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.
²³ 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.
²⁴ Institute for Social Research, University of Michigan, Ann Arbor, Michigan.
²⁵ Translational Gerontology Branch, National Institute on Aging, Baltimore, Maryland.
²⁶ Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas.
²⁷ Department of Psychiatry, Trinity Centre for Health Science, Dublin, Ireland.
²⁸ QIMR Berghofer Medical Research Institute, Brisbane.
²⁹ 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.
³⁰ Department of Psychiatry, Neuroscience Campus Amsterdam and EMGO Institute of Health and Care Research, VU University, Amsterdam, The Netherlands.
³¹ Department of Psychiatry, Kaiser Permanente San Francisco Medical Center, San Francisco.
³² Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen.
³³ Department of Psychiatry, Washington University, St. Louis, Missouri.
³⁴ Department of Epidemiology, Erasmus University Medical Center, Rotterdam; Department of Psychiatry, Erasmus University Medical Center, Rotterdam.
³⁵ Department of Epidemiology, Erasmus University Medical Center, Rotterdam.
³⁶ Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Munich.
³⁷ 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.
³⁸ Max Planck Institute of Psychiatry, Munich.
³⁹ Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York.
⁴⁰ Institute of Social and Preventive Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne.
⁴¹ 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.
⁴² Folkhalsan Research Centre, Helsinki; Institute of Behavioural Sciences, University of Helsinki, Helsinki.
⁴³ Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, California.
⁴⁴ Division of Psychiatry, University College London, London.
⁴⁵ Janssen Research & Development LLC, New Brunswick, New Jersey.
⁴⁶ University of Exeter Medical School, Exeter.
⁴⁷ 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.
⁴⁸ Estonian Genome Center, University of Tartu, Tartu, Estonia; Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
⁴⁹ The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus; Research Department P, Aarhus University Hospital, Risskov, Denmark.
⁵⁰ Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi.
⁵¹ 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.
⁵² Max Planck Institute of Psychiatry, Munich; Munich Cluster for Systems Neurology, Munich; University of Liverpool, Institute of Translational Medicine, Liverpool.
⁵³ Institute of Human Genetics, University of Bonn, Bonn; Department of Genomics, Life & Brain Center, Bonn.
⁵⁴ QIMR Berghofer Medical Research Institute, Brisbane; Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland.
⁵⁵ MRC Centre for Neuropsychiatric Genetics and Genomics, Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, United Kingdom.
⁵⁶ Department of Psychiatry, Washington University, St. Louis, Missouri; Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, Florida.
⁵⁷ Center for Experimental Drugs and Diagnostics, Massachusetts General Hospital and Harvard Medical School, Boston.
⁵⁸ Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, Iowa.
⁵⁹ Division of Psychiatric Genomics, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York.
⁶⁰ 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.
⁶¹ Institute of Behavioural Sciences, University of Helsinki, Helsinki.
⁶² Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim.
⁶³ 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.
⁶⁴ Institute of Psychiatric Phenomics and Genomics, Ludwig-Maximilians-University, Munich; Department of Psychiatry and Psychotherapy, University of Göttingen, Göttingen, Germany.
⁶⁵ Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
⁶⁶ Group Health, Seattle, Washington.
⁶⁷ Department of Psychiatry and Psychiatric Neuroscience, School of Medicine and Dentistry, James Cook University, Townsville, Queensland, Australia.
⁶⁸ Unit of Genetic Epidemiology & Bioinformatics, University Medical Center Groningen, University of Groningen, Groningen.
⁶⁹ Institute for Community Medicine, University Medicine Greifswald, Greifswald, Munich.
⁷⁰ MRC Social, Genetic & Developmental Psychiatry Centre Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London; Dalhousie University, Halifax, Nova Scotia, Canada.
⁷¹ Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Munich; German Center for Neurodegenerative Diseases, Site Rostock/Greifswald, Munich.
⁷² Department of Epidemiology, University of Michigan, Ann Arbor, Michigan; Institute for Social Research, University of Michigan, Ann Arbor, Michigan.
⁷³ College of Physicians and Surgeons, Columbia University and New York State Psychiatric Institute, New York, New York.
⁷⁴ Department of Epidemiology, Erasmus University Medical Center, Rotterdam; Department of Psychiatry, Erasmus University Medical Center, Rotterdam. Electronic address: h.tiemeier@erasmusmc.nl.
⁷⁵ 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.

PMID: 28049566
PMCID: PMC5462867
DOI: 10.1016/j.biopsych.2016.11.013

Abstract

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: 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: 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: 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.

Keywords: CHARGE consortium; Depressive symptoms; FHIT gene; Genome-wide association study; Major depressive disorder; Psychiatric Genomics Consortium.

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Conflict of interest statement

Conflict of Interest: The other authors report no conflicts.

Figures

**Figure 1. Manhattan Plot**
X-axis represents the chromosomal position for each SNP, and y-axis the −log10 P value for association with depression.

See this image and copyright information in PMC

Comment in

A Genetic Locus Associated With Depression: The Iceberg Begins to Melt.
Nurnberger JI Jr. Nurnberger JI Jr. Biol Psychiatry. 2017 Sep 1;82(5):304-305. doi: 10.1016/j.biopsych.2017.06.023. Biol Psychiatry. 2017. PMID: 28781002 No abstract available.

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An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype

Affiliations

An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

Comment in

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources