SynthesisBiological psychiatry2020
Classical Human Leukocyte Antigen Alleles and C4 Haplotypes Are Not Significantly Associated With Depression.
Open access · hybridAbstract readMeta-Analysis
In one paragraph
Synthesis in Biological psychiatry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
1.5field-weighted citation impact, top 20% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Investigating the relationship between depression and breast cancer: observational and genetic analyses.BMC medicine · 2023Pooled it
- Genomics of schizophrenia, bipolar disorder and major depressive disorder.Nature reviews. Genetics · 2025Review
- HLA Class II Alleles and Suicidal Behavior: Evidence from a Case-Control Study.International journal of molecular sciences · 2025Article
- Haplotype analysis reveals pleiotropic disease associations in the HLA region.American journal of human genetics · 2025Article
- Overexpression of OTX2 in human neural cells links depression risk genes.Translational psychiatry · 2025Article
- Unique genetic and risk-factor profiles in clusters of major depressive disorder-related multimorbidity trajectories.Nature communications · 2024Article
- Evaluating 17 methods incorporating biological function with GWAS summary statistics to accelerate discovery demonstrates a tradeoff between high sensitivity and high positive predictive value.Communications biology · 2023Article
- Multi-ancestry phenome-wide association of complement component 4 variation with psychiatric and brain phenotypes in youth.Genome biology · 2023Article
- Saliva microbiome, dietary, and genetic markers are associated with suicidal ideation in university students.Scientific reports · 2022Article
- Deep learning-based integration of genetics with registry data for stratification of schizophrenia and depression.Science advances · 2022Article
- The role of critical immune genes in brain disorders: insights from neuroimaging immunogenetics.Brain communications · 2022Article
- Sensitive period-regulating genetic pathways and exposure to adversity shape risk for depression.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Article
- Evaluation of polygenic prediction methodology within a reference-standardized framework.PLoS genetics · 2021Article
- Review
- Understanding the genetic contribution of the human leukocyte antigen system to common major psychiatric disorders in a world pandemic context.Brain, behavior, and immunity · 2021Review
- Potential Genes and Mechanisms Linking Intracerebral Hemorrhage and Depression: A Bioinformatics-Based Study.International journal of general medicine · 2021Article
- Immune dysregulation in depression: Evidence from genome-wide association.Brain, behavior, & immunity - health · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
54 authors at 20 institutions in 11 countries.
Kylie P GlanvilleSocial Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom. Electronic address: kylie.glanville@kcl.ac.uk.
Jonathan R I ColemanSocial Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom; National Institute for Health Research Biomedical Research Centre South London and Maudsley National Health Service Trust, King's College London, London, United Kingdom.
Ken B HanscombeDepartment of Medical and Molecular Genetics, King's College London, London, United Kingdom.
Jack EuesdenSocial Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
Shing Wan ChoiSocial Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom; Genetics and Genomic Sciences, Icahn School of Medicine, Mount Sinai, New York, New York.
Kirstin L PurvesSocial Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
Gerome BreenSocial Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom; National Institute for Health Research Biomedical Research Centre South London and Maudsley National Health Service Trust, King's College London, London, United Kingdom.
Tracy M AirDiscipline of Psychiatry, Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.
Till F M AndlauerDepartment of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Münster, Germany; Munich Cluster for Systems Neurology (SyNergy), Münster, Germany.
Bernhard T BauneDepartment of Psychiatry, Melbourne Medical School, University of Melbourne, Melbourne, Victoria, Australia; Florey Institute for Neuroscience and Mental Health, University of Melbourne, Melbourne, Victoria, Australia; Department of Psychiatry, University of Münster, Münster, Germany.
Elisabeth B BinderDepartment of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Emory University, Atlanta, Georgia; Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Münster, Germany.
Douglas H R BlackwoodDivision of Psychiatry, University of Edinburgh, Edinburgh, United Kingdom.
Dorret I BoomsmaDepartment of Biological Psychology and EMGO+ Institute for Health and Care Research, Vrije Universiteit Medical Center, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Henriette N ButtenschønNIDO | Danmark, Regional Hospital West Jutland, Herning, Denmark; iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Denmark.
Lucía Colodro-CondeGenetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Udo DannlowskiDepartment of Psychiatry, University of Münster, Münster, Germany.
Nese DirekEpidemiology, Erasmus Medical Center, Rotterdam, The Netherlands; Department of Psychiatry, Dokuz Eylul University School Of Medicine, Izmir, Turkey.
Erin C DunnDepartment of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts; Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts; Stanley Center for Psychiatric Research, Broad Institute, Cambridge, Massachusetts.
Andreas J ForstnerInstitute of Human Genetics, School of Medicine and University Hospital Bonn, University of Bonn, Bonn, Germany; Centre for Human Genetics, University of Marburg, Marburg, Germany; Department of Psychiatry, University of Basel, Basel, Switzerland; Department of Biomedicine, University of Basel, Basel, Switzerland.
Eco J C de GeusDepartment of Biological Psychology and EMGO+ Institute for Health and Care Research, Vrije Universiteit Medical Center, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands; Amsterdam Public Health Institute, Vrije Universiteit Medical Center, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Hans J GrabeDepartment of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
Steven P HamiltonDepartment of Psychiatry, Kaiser Permanente Northern California, San Francisco, California.
Ian JonesMedical Research Council Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, United Kingdom.
Lisa A JonesDepartment of Psychological Medicine, University of Worcester, Worcester, United Kingdom.
James A KnowlesPsychiatry and the Behavioral Sciences, University of Southern California, Los Angeles, California.
Zoltán KutalikInstitute of Social and Preventive Medicine, University Hospital of Lausanne, Lausanne, Switzerland; Swiss Institute of Bioinformatics, Lausanne, Switzerland.
Douglas F LevinsonPsychiatry and Behavioral Sciences, Stanford University, Stanford, California.
Glyn LewisDivision of Psychiatry, University College London, London, United Kingdom.
Penelope A LindGenetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Susanne LucaeMax Planck Institute of Psychiatry, Munich, Germany.
Patrik K MagnussonDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Peter McGuffinSocial Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
Andrew M McIntoshDivision of Psychiatry, University of Edinburgh, Edinburgh, United Kingdom; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom.
Yuri MilaneschiDepartment of Psychiatry, Amsterdam Universiteit Medical Center, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Ole MorsiPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Denmark; Psychosis Research Unit, Aarhus University Hospital, Risskov, Aarhus, Denmark.
Sara MostafaviDepartment of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada; Department of Statistics, University of British Columbia, Vancouver, British Columbia, Canada.
Bertram Müller-MyhsokUniversity of Liverpool, Liverpool, United Kingdom; Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Münster, Germany; Munich Cluster for Systems Neurology (SyNergy), Münster, Germany.
Nancy L PedersenDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Brenda W J H PenninxDepartment of Psychiatry, Amsterdam Universiteit Medical Center, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
James B PotashPsychiatry, University of Iowa, Iowa City, Iowa.
Martin PreisigDepartment of Psychiatry, University Hospital of Lausanne, Prilly, Switzerland.
Stephan RipkeAnalytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts; Department of Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts; Department of Psychiatry and Psychotherapy, Universitätsmedizin Berlin Campus Charité Mitte, Berlin, Germany.
Jianxin ShiDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
Stanley I ShynBehavioral Health Services, Kaiser Permanente Washington, Seattle, Washington.
Jordan W SmollerDepartment of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts; Psychiatric and Neurodevelopmental Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts; Stanley Center for Psychiatric Research, Broad Institute, Cambridge, Massachusetts.
Fabian StreitDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Patrick F SullivanDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Henning TiemeierEpidemiology, Erasmus Medical Center, Rotterdam, The Netherlands; Child and Adolescent Psychiatry, Erasmus Medical Center, Rotterdam, The Netherlands; Psychiatry, Erasmus Medical Center, Rotterdam, The Netherlands.
Rudolf UherDepartment of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada.
Sandra Van der AuweraDepartment of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
Myrna M WeissmanDivision of Epidemiology, New York State Psychiatric Institute, New York, New York; Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, New York.
Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium
Paul F O'ReillySocial Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom; Genetics and Genomic Sciences, Icahn School of Medicine, Mount Sinai, New York, New York.
Cathryn M LewisSocial Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom; Department of Medical and Molecular Genetics, King's College London, London, United Kingdom.
King's College London · GBKarolinska Institutet · SEBroad Institute · USUniversity of North Carolina at Chapel Hill · USKaiser Permanente · USUniversitätsmedizin Greifswald · DEVrije Universiteit Amsterdam · NLNational Cancer Institute · USQIMR Berghofer Medical Research Institute · AUCardiff University · GBNational Health Service · GBUniversity Hospital of Lausanne · CHUniversity of British Columbia · CAAmsterdam Public Health · NLDalhousie University · CADokuz Eylül University · TREmory University · USErasmus MC · NLHeidelberg University · DELundbeck Foundation · DK
Funding
International Cohort Collection for Bipolar DisorderR01MH085542 · NIMH · MASSACHUSETTS GENERAL HOSPITAL · PI SMOLLER, JORDAN W · 2008 to 2012
$10.7MMOLECULAR GENETICS OF SCHIZOPHRENIAR01MH059571 · NIMH · UNIVERSITY OF CHICAGO · PI GEJMAN, PABLO V. · 1999 to 2007
$8.0MIntegration of Genomics & Transcriptomics in Normal Twins & Major DepressionRC2MH089951 · NIMH · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SULLIVAN, PATRICK F · 2009 to 2010
$6.5MPharmacogenomics of Antidepressant ResponseR01MH072802 · NIMH · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI HAMILTON, STEVEN P. · 2005 to 2008
$4.6MA Genome-Wide Association Study of SchizophreniaU01MH079469 · NIMH · NORTHSHORE UNIVERSITY HEALTHSYSTEM · PI GEJMAN, PABLO V. · 2007 to 2009
$4.4MGenomics of Developmental Trajectories in TwinsRC2MH089995 · NIMH · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI HUDZIAK, JAMES J. · 2009 to 2010
$3.8M1/7 PGC: Advancing Discovery and ImpactR01MH124871 · NIMH · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BULIK, CYNTHIA M, SULLIVAN, PATRICK F · 2021 to 2025
$3.5M7/7 Psychiatric Genomics Consortium: Finding actionable variationU01MH109532 · NIMH · WASHINGTON UNIVERSITY · PI AGRAWAL, ARPANA, EDENBERG, HOWARD J · 2016 to 2020
$3.1MMOLECULAR GENETICS OF SCHIZOPHRENIAR01MH060879 · NIMH · WASHINGTON UNIVERSITY · PI CLONINGER, C. ROBERT · 1999 to 2006
$2.7M3/7 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
$2.5MGenetic Epideniologic Models of Alcohol AbuseR37AA007728 · NIAAA · WASHINGTON UNIVERSITY · PI HEATH, ANDREW C. · 1998 to 2007
$2.2MEPA EP-C-15-001Medical Research Council G0200243Medical Research Council G0701420Medical Research Council G0901245Medical Research Council MC_PC_17228Medical Research Council MC_QA137853Medical Research Council MC_UU_00007/10Medical Research Council MR/L010305/1Medical Research Council MR/L023784/2Medical Research Council MR/N015746/1NIAAA NIH HHS R01 AA007535NIAAA NIH HHS R01 AA007728NIAAA NIH HHS R01 AA010249NIAAA NIH HHS R37 AA007728NIMH NIH HHS K01 MH113848NIMH NIH HHS R01 MH059565NIMH NIH HHS R01 MH059566NIMH NIH HHS R01 MH059571NIMH NIH HHS R01 MH059586NIMH NIH HHS R01 MH059587NIMH NIH HHS R01 MH059588NIMH NIH HHS R01 MH060870NIMH NIH HHS R01 MH060879NIMH NIH HHS R01 MH061675NIMH NIH HHS R01 MH067257NIMH NIH HHS R01 MH072802NIMH NIH HHS R01 MH081800NIMH NIH HHS R01 MH085542NIMH NIH HHS R01 MH086026NIMH NIH HHS R01 MH124871NIMH NIH HHS RC2 MH089951NIMH NIH HHS RC2 MH089995NIMH NIH HHS U01 MH046276NIMH NIH HHS U01 MH046318NIMH NIH HHS U01 MH079469NIMH NIH HHS U01 MH079470NIMH NIH HHS U01 MH109528NIMH NIH HHS U01 MH109532NIMH NIH HHS U01 MH109536Wellcome Trust
Abstract
backgroundThe prevalence of depression is higher in individuals with autoimmune diseases, but the mechanisms underlying the observed comorbidities are unknown. Shared genetic etiology is a plausible explanation for the overlap, and in this study we tested whether genetic variation in the major histocompatibility complex (MHC), which is associated with risk for autoimmune diseases, is also associated with risk for depression.
methodsWe fine-mapped the classical MHC (chr6: 29.6-33.1 Mb), imputing 216 human leukocyte antigen (HLA) alleles and 4 complement component 4 (C4) haplotypes in studies from the Psychiatric Genomics Consortium Major Depressive Disorder Working Group and the UK Biobank. The total sample size was 45,149 depression cases and 86,698 controls. We tested for association between depression status and imputed MHC variants, applying both a region-wide significance threshold (3.9 × 10
resultsNo HLA alleles or C4 haplotypes were associated with depression at the region-wide threshold. HLA-B*08:01 was associated with modest protection for depression at the candidate threshold for testing in HLA genes in the meta-analysis (odds ratio = 0.98, 95% confidence interval = 0.97-0.99).
conclusionsWe found no evidence that an increased risk for depression was conferred by HLA alleles, which play a major role in the genetic susceptibility to autoimmune diseases, or C4 haplotypes, which are strongly associated with schizophrenia. These results suggest that any HLA or C4 variants associated with depression either are rare or have very modest effect sizes.
Indexed as
Major Depressive DisorderAllelesDepressionGenetic Predisposition to DiseaseHaplotypesHLA AntigensHumansMajor Histocompatibility ComplexHLA AntigensAutoimmune disorderComplementGenetic associationHuman leukocyte antigenMajor depressive disorderMajor histocompatibility complex
Identifiers
What OpenQuestion holds
Textmetadata
LicenceCC BY
Read underepoch 390
Registered trials
None linked
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.