SynthesisNature neuroscience2019
Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions.
Open access · greenAbstract readMeta-Analysis
In one paragraph
Synthesis in Nature neuroscience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1,429 papers, 10 of them syntheses that pooled it.
0numbers the graph read from it
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1,429citing papers in PubMed, 10 pooled it
206.5field-weighted citation impact, top 1% of its field
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1,429 citing papers in PubMed, 10 syntheses or guidelines pooled it, 2,722 citations in OpenAlex.
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- Article
1,369 more citing papers are in PubMed but not listed here.
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Authors and funding
40 authors at 12 institutions in 5 countries.
David M HowardDivision of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK. D.Howard@ed.ac.uk.ORCID http://orcid.org/0000-0002-6005-1972
Mark J AdamsDivision of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK.ORCID http://orcid.org/0000-0002-3599-6018
Toni-Kim ClarkeDivision of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK.
Jonathan D HaffertyDivision of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK.
Jude GibsonDivision of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK.ORCID http://orcid.org/0000-0002-3745-8360
Masoud ShiraliDivision of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK.ORCID http://orcid.org/0000-0002-5401-0541
Jonathan R I ColemanSocial Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.ORCID http://orcid.org/0000-0002-6759-0944
Saskia P HagenaarsSocial Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
Joey WardInstitute of Health and Wellbeing, University of Glasgow, Glasgow, UK.
Eleanor M WigmoreDivision of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK.
Clara AllozaDivision of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK.ORCID http://orcid.org/0000-0002-2092-8055
Xueyi ShenDivision of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK.ORCID http://orcid.org/0000-0002-0538-4774
Miruna C BarbuDivision of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK.
Eileen Y XuDivision of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK.
Heather C WhalleyDivision of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK.ORCID http://orcid.org/0000-0002-4505-8869
Riccardo E MarioniCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
David J PorteousCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.ORCID http://orcid.org/0000-0003-1249-6106
Gail DaviesCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
Ian J DearyCentre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
Gibran HemaniMedical Research Council (MRC) Integrative Epidemiology Unit, Population Health, Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Klaus BergerInstitute of Epidemiology & Social Medicine, University of Münster, Münster, Germany.
Henning TeismannInstitute of Epidemiology & Social Medicine, University of Münster, Münster, Germany.ORCID http://orcid.org/0000-0001-5807-5572
Rajesh RawalInstitute of Epidemiology & Social Medicine, University of Münster, Münster, Germany.
Volker AroltDepartment of Psychiatry, University of Münster, Münster, Germany.
Bernhard T BauneDepartment of Psychiatry, University of Melbourne, Victoria, Australia.
Udo DannlowskiDepartment of Psychiatry, University of Münster, Münster, Germany.
Katharina DomschkeDepartment of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Chao Tian23andMe, Inc, Mountain View, CA, USA.
David A Hinds23andMe, Inc, Mountain View, CA, USA.ORCID http://orcid.org/0000-0002-4911-803X
23andMe Research Team
Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium
Maciej TrzaskowskiQueensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.
Enda M ByrneQueensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.ORCID http://orcid.org/0000-0002-9491-7797
Stephan RipkeDepartment of Psychiatry, Charite Universitatsmedizin Berlin Campus Benjamin Franklin, Berlin, Germany.
Daniel J SmithInstitute of Health and Wellbeing, University of Glasgow, Glasgow, UK.ORCID http://orcid.org/0000-0002-2267-1951
Patrick F SullivanDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Naomi R WrayQueensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia.ORCID http://orcid.org/0000-0001-7421-3357
Gerome BreenSocial Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.ORCID http://orcid.org/0000-0003-2053-1792
Cathryn M LewisSocial Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.ORCID http://orcid.org/0000-0002-8249-8476
Andrew M McIntoshDivision of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK.ORCID http://orcid.org/0000-0002-0198-4588
Royal Edinburgh Hospital · GBUniversity of Münster · DEKing's College London · GBUniversity of Edinburgh · GBThe University of Queensland · AU23andMe (United States) · USUniversity of Glasgow · GBBroad Institute · USThe University of Melbourne · AUUniversity of Bristol · GBUniversity of Freiburg · DEUniversity of North Carolina at Chapel Hill · US
Funding
TOXICOLOGY OF ENVIRONMENTAL HALOCARBONSP01ES000040 · NIEHS · OREGON STATE UNIVERSITY · PI KERKVLIET, NANCY I · 1985 to 2007
$8.0M7/7 Psychiatric Genomics Consortium: Finding actionable variationU01MH109532 · NIMH · WASHINGTON UNIVERSITY · PI AGRAWAL, ARPANA, EDENBERG, HOWARD J · 2016 to 2020
$3.1M3/7 Psychiatric Genomics Consortium: Finding actionable variationU01MH109536 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI CHARNEY, ALEXANDER W, HUCKINS, LAURA MARIANNE · 2016 to 2020
$2.7M1/7 Psychiatric Genomics Consortium: Finding actionable variationU01MH109528 · NIMH · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SULLIVAN, PATRICK F · 2016 to 2020
$2.5MMedical Research Council G0700704Medical Research Council MC_PC_17209Medical Research Council MC_PC_17228Medical Research Council MC_QA137853Medical Research Council MR/J000914/1Medical Research Council MR/K026992/1Medical Research Council MR/S015132/1MRF_ C0396NIEHS NIH HHS P01 ES000040NIMH NIH HHS U01 MH109528NIMH NIH HHS U01 MH109532NIMH NIH HHS U01 MH109536Wellcome Trust 104036Wellcome Trust 208806
Abstract
Major depression is a debilitating psychiatric illness that is typically associated with low mood and anhedonia. Depression has a heritable component that has remained difficult to elucidate with current sample sizes due to the polygenic nature of the disorder. To maximize sample size, we meta-analyzed data on 807,553 individuals (246,363 cases and 561,190 controls) from the three largest genome-wide association studies of depression. We identified 102 independent variants, 269 genes, and 15 genesets associated with depression, including both genes and gene pathways associated with synaptic structure and neurotransmission. An enrichment analysis provided further evidence of the importance of prefrontal brain regions. In an independent replication sample of 1,306,354 individuals (414,055 cases and 892,299 controls), 87 of the 102 associated variants were significant after multiple testing correction. These findings advance our understanding of the complex genetic architecture of depression and provide several future avenues for understanding etiology and developing new treatment approaches.
Indexed as
Cohort StudiesDepressionFemaleGenetic Predisposition to DiseaseGenetic VariationGenome-Wide Association StudyHumansMajor Depressive DisorderMaleMultifactorial InheritancePolymorphism, Single NucleotidePrefrontal Cortex
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