Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression
Major depressive disorder (MDD) is a common illness accompanied by considerable morbidity, mortality, costs, and heightened risk of suicide. We conducted a genome-wide association meta-analysis based in 135,458 cases and 344,901 controls and identified 44 independent and significant loci. The geneti...
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| Vydáno v: | Nature genetics Ročník 50; číslo 5; s. 668 - 681 |
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| Médium: | Journal Article |
| Jazyk: | angličtina |
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New York
Nature Publishing Group US
01.05.2018
Nature Publishing Group |
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| ISSN: | 1061-4036, 1546-1718, 1546-1718 |
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| Abstract | Major depressive disorder (MDD) is a common illness accompanied by considerable morbidity, mortality, costs, and heightened risk of suicide. We conducted a genome-wide association meta-analysis based in 135,458 cases and 344,901 controls and identified 44 independent and significant loci. The genetic findings were associated with clinical features of major depression and implicated brain regions exhibiting anatomical differences in cases. Targets of antidepressant medications and genes involved in gene splicing were enriched for smaller association signal. We found important relationships of genetic risk for major depression with educational attainment, body mass, and schizophrenia: lower educational attainment and higher body mass were putatively causal, whereas major depression and schizophrenia reflected a partly shared biological etiology. All humans carry lesser or greater numbers of genetic risk factors for major depression. These findings help refine the basis of major depression and imply that a continuous measure of risk underlies the clinical phenotype.
A genome-wide association meta-analysis of individuals with clinically assessed or self-reported depression identifies 44 independent risk loci. Comparisons with other psychiatric disorders and candidate gene analyses provide new insights into major depressive disorder. |
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| AbstractList | Major depressive disorder (MDD) is a common illness accompanied by considerable morbidity, mortality, costs, and heightened risk of suicide. We conducted a genome-wide association meta-analysis based in 135,458 cases and 344,901 controls and identified 44 independent and significant loci. The genetic findings were associated with clinical features of major depression and implicated brain regions exhibiting anatomical differences in cases. Targets of antidepressant medications and genes involved in gene splicing were enriched for smaller association signal. We found important relationships of genetic risk for major depression with educational attainment, body mass, and schizophrenia: lower educational attainment and higher body mass were putatively causal, whereas major depression and schizophrenia reflected a partly shared biological etiology. All humans carry lesser or greater numbers of genetic risk factors for major depression. These findings help refine the basis of major depression and imply that a continuous measure of risk underlies the clinical phenotype.Major depressive disorder (MDD) is a common illness accompanied by considerable morbidity, mortality, costs, and heightened risk of suicide. We conducted a genome-wide association meta-analysis based in 135,458 cases and 344,901 controls and identified 44 independent and significant loci. The genetic findings were associated with clinical features of major depression and implicated brain regions exhibiting anatomical differences in cases. Targets of antidepressant medications and genes involved in gene splicing were enriched for smaller association signal. We found important relationships of genetic risk for major depression with educational attainment, body mass, and schizophrenia: lower educational attainment and higher body mass were putatively causal, whereas major depression and schizophrenia reflected a partly shared biological etiology. All humans carry lesser or greater numbers of genetic risk factors for major depression. These findings help refine the basis of major depression and imply that a continuous measure of risk underlies the clinical phenotype. Major depressive disorder (MDD) is a common illness accompanied by considerable morbidity, mortality, costs, and heightened risk of suicide. We conducted a genome-wide association meta-analysis based in 135,458 cases and 344,901 controls and identified 44 independent and significant loci. The genetic findings were associated with clinical features of major depression and implicated brain regions exhibiting anatomical differences in cases. Targets of antidepressant medications and genes involved in gene splicing were enriched for smaller association signal. We found important relationships of genetic risk for major depression with educational attainment, body mass, and schizophrenia: lower educational attainment and higher body mass were putatively causal, whereas major depression and schizophrenia reflected a partly shared biological etiology. All humans carry lesser or greater numbers of genetic risk factors for major depression. These findings help refine the basis of major depression and imply that a continuous measure of risk underlies the clinical phenotype. A genome-wide association meta-analysis of individuals with clinically assessed or self-reported depression identifies 44 independent risk loci. Comparisons with other psychiatric disorders and candidate gene analyses provide new insights into major depressive disorder. Major depressive disorder (MDD) is a common illness accompanied by considerable morbidity, mortality, costs, and heightened risk of suicide. We conducted a genome-wide association meta-analysis based in 135,458 cases and 344,901 controls and identified 44 independent and significant loci. The genetic findings were associated with clinical features of major depression and implicated brain regions exhibiting anatomical differences in cases. Targets of antidepressant medications and genes involved in gene splicing were enriched for smaller association signal. We found important relationships of genetic risk for major depression with educational attainment, body mass, and schizophrenia: lower educational attainment and higher body mass were putatively causal, whereas major depression and schizophrenia reflected a partly shared biological etiology. All humans carry lesser or greater numbers of genetic risk factors for major depression. These findings help refine the basis of major depression and imply that a continuous measure of risk underlies the clinical phenotype. Major depressive disorder (MDD) is a common illness accompanied by considerable morbidity, mortality, costs, and heightened risk of suicide. We conducted a genome-wide association (GWA) meta-analysis based in 135,458 cases and 344,901 control, We identified 44 independent and significant loci. The genetic findings were associated with clinical features of major depression, and implicated brain regions exhibiting anatomical differences in cases. Targets of antidepressant medications and genes involved in gene splicing were enriched for smaller association signal. We found important relations of genetic risk for major depression with educational attainment, body mass, and schizophrenia: lower educational attainment and higher body mass were putatively causal whereas major depression and schizophrenia reflected a partly shared biological etiology. All humans carry lesser or greater numbers of genetic risk factors for major depression. These findings help refine and define the basis of major depression and imply a continuous measure of risk underlies the clinical phenotype. |
| Author | Hougaard, David M. Domschke, Katharina Weinsheimer, Shantel Marie Strohmaier, Jana Hamilton, Steven P. Mors, Ole Peterson, Roseann E. Wray, Naomi R. Bybjerg-Grauholm, Jonas Witt, Stephanie H. Mihailov, Evelin Mill, Jonathan Smoller, Jordan W. Stockmeier, Craig A. MacIntyre, Donald J. Eley, Thalia C. Lu, Leina Maier, Robert M. Herms, Stefan Milaneschi, Yuri Potash, James B. Air, Tracy M. Mattheisen, Manuel Degenhardt, Franziska Lane, Jacqueline M. Winslow, Ashley R. Horn, Carsten O’Donovan, Michael C. Escott-Price, Valentina Gordon, Scott D. Lind, Penelope A. Martin, Nicholas G. Baune, Bernhard T. Dunn, Erin C. Forstner, Andreas J. Giusti-Rodríguez, Paola Buttenschøn, Henriette N. Krogh, Jesper Maier, Wolfgang Wellmann, Jürgen Thorgeirsson, Thorgeir E. Shyn, Stanley I. Binder, Elisabeth B. Kohane, Isaac S. Schaefer, Catherine Liu, Xiaoxiao Sinnamon, Grant B. C. Tiemeier, Henning Ising, Marcus Mehta, Divya Pedersen, Carsten Bøcker Owen, Michael J. Stefansson, Hreinn Werge, Thomas Zhang, Futao Nöthen, Markus M. Schulze, Thomas G. Weissman, Myrn |
| AuthorAffiliation | 13 National Centre for Register-Based Research, Aarhus University, Aarhus, DK 51 Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Baden-Württemberg, DE 92 Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Mecklenburg-Vorpommern, DE 46 Bioinformatics, University of British Columbia, Vancouver, BC, CA 104 Department of Psychiatry and Psychotherapy, Medical Center of the University of Munich, Campus Innenstadt, Munich, DE 111 deCODE Genetics / Amgen, Reykjavik, IS 155 Department of Clinical Medicine, University of Copenhagen, Copenhagen, DK 105 Institute of Psychiatric Phenomics and Genomics (IPPG), Medical Center of the University of Munich, Campus Innenstadt, Munich, DE 70 Division of Research, Kaiser Permanente Northern California, Oakland, CA, US 102 Department of Biochemistry and Molecular Biology II, Institute of Neurosciences, Center for Biomedic |
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J. organization: Department of Biological Psychology and EMGO+ Institute for Health and Care Research, Vrije Universiteit Amsterdam, Amsterdam Public Health Institute, Vrije Universiteit Medical Center – sequence: 173 givenname: Katharina surname: Domschke fullname: Domschke, Katharina organization: Department of Psychiatry and Psychotherapy, Medical Center, Faculty of Medicine, University of Freiburg – sequence: 174 givenname: Tõnu surname: Esko fullname: Esko, Tõnu organization: Medical and Population Genetics, Broad Institute, Estonian Genome Center, University of Tartu – sequence: 179 givenname: David A. surname: Hinds fullname: Hinds, David A. organization: Research, 23andMe, Inc – sequence: 183 givenname: Qingqin S. surname: Li fullname: Li, Qingqin S. organization: Neuroscience Therapeutic Area, Janssen Research and Development, LLC – sequence: 188 givenname: Andrew M. surname: McIntosh fullname: McIntosh, Andrew M. organization: Division of Psychiatry, University of Edinburgh, Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh – sequence: 189 givenname: Andres surname: Metspalu fullname: Metspalu, Andres organization: Estonian Genome Center, University of Tartu, Institute of Molecular and Cell Biology, University of Tartu – sequence: 190 givenname: Ole surname: Mors fullname: Mors, Ole organization: iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Psychosis Research Unit, Aarhus University Hospital, Risskov – sequence: 192 givenname: Bertram surname: Müller-Myhsok fullname: Müller-Myhsok, Bertram organization: Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Munich Cluster for Systems Neurology (SyNergy), Institute of Translational Medicine, University of Liverpool – sequence: 195 givenname: Michael C. surname: O’Donovan fullname: O’Donovan, Michael C. organization: MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University – sequence: 196 givenname: Sara A. surname: Paciga fullname: Paciga, Sara A. organization: Human Genetics and Computational Biomedicine, Pfizer Global Research and Development – sequence: 197 givenname: Nancy L. surname: Pedersen fullname: Pedersen, Nancy L. organization: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet – sequence: 199 givenname: Roy H. surname: Perlis fullname: Perlis, Roy H. organization: Department of Psychiatry, Massachusetts General Hospital, Psychiatry, Harvard Medical School – sequence: 201 givenname: James B. surname: Potash fullname: Potash, James B. organization: Psychiatry, University of Iowa – sequence: 204 givenname: Catherine surname: Schaefer fullname: Schaefer, Catherine organization: Division of Research, Kaiser Permanente Northern California – sequence: 205 givenname: Thomas G. surname: Schulze fullname: Schulze, Thomas G. organization: Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Psychiatry and Behavioral Sciences, Johns Hopkins University, Institute of Psychiatric Phenomics and Genomics (IPPG), Medical Center of the University of Munich, Campus Innenstadt, Human Genetics Branch, NIMH Division of Intramural Research Programs, Department of Psychiatry and Psychotherapy, University Medical Center Göttingen – sequence: 209 givenname: Rudolf surname: Uher fullname: Uher, Rudolf organization: Psychiatry, Dalhousie University – sequence: 210 givenname: Henry surname: Völzke fullname: Völzke, Henry organization: Institute for Community Medicine, University Medicine Greifswald – sequence: 213 givenname: Ashley R. surname: Winslow fullname: Winslow, Ashley R. organization: Human Genetics and Computational Biomedicine, Pfizer Global Research and Development, Perelman School of Medicine, University of Pennsylvania – sequence: 217 givenname: Anders D. surname: Børglum fullname: Børglum, Anders D. organization: Department of Biomedicine, Aarhus University, iSEQ, Centre for Integrative Sequencing, Aarhus University, iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/29700475$$D View this record in MEDLINE/PubMed http://kipublications.ki.se/Default.aspx?queryparsed=id:138214594$$DView record from Swedish Publication Index (Karolinska Institutet) |
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| ContentType | Journal Article |
| Copyright | The Author(s) 2018 Copyright Nature Publishing Group May 2018 |
| Copyright_xml | – notice: The Author(s) 2018 – notice: Copyright Nature Publishing Group May 2018 |
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| Snippet | Major depressive disorder (MDD) is a common illness accompanied by considerable morbidity, mortality, costs, and heightened risk of suicide. We conducted a... |
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| SubjectTerms | 692/308/2056 692/699/476 Agriculture Animal Genetics and Genomics Biomedical and Life Sciences Biomedicine Body mass Body size Brain Cancer Research Case-Control Studies Consortia Deoxyribonucleic acid Depressive Disorder, Major - genetics DNA DNA methylation Education Educational attainment Etiology Female Gene expression Gene Function Gene loci Genetic Predisposition to Disease Genome-Wide Association Study - methods Genomes Genomics Human Genetics Humans Liability Male Mental depression Mental disorders Meta-analysis Morbidity Multifactorial Inheritance Phenotype Phenotypes Polymorphism, Single Nucleotide Risk analysis Risk Factors Schizophrenia Schizophrenia - genetics Splicing Suicide |
| Title | Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression |
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