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Classical Human Leukocyte Antigen Alleles and C4 Haplotypes Are Not Significantly Associated With Depression.

Authors
  • Glanville, Kylie P1
  • Coleman, Jonathan R I2
  • Hanscombe, Ken B3
  • Euesden, Jack4
  • Choi, Shing Wan5
  • Purves, Kirstin L4
  • Breen, Gerome2
  • Air, Tracy M6
  • Andlauer, Till F M7
  • Baune, Bernhard T8
  • Binder, Elisabeth B9
  • Blackwood, Douglas H R10
  • Boomsma, Dorret I11
  • Buttenschøn, Henriette N12
  • Colodro-Conde, Lucía13
  • Dannlowski, Udo14
  • Direk, Nese15
  • Dunn, Erin C16
  • Forstner, Andreas J17
  • de Geus, Eco J C18
  • And 33 more
  • 1 Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom. Electronic address: [email protected] , (United Kingdom)
  • 2 Social 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. , (United Kingdom)
  • 3 Department of Medical and Molecular Genetics, King's College London, London, United Kingdom. , (United Kingdom)
  • 4 Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom. , (United Kingdom)
  • 5 Social 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. , (United Kingdom)
  • 6 Discipline of Psychiatry, Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia. , (Australia)
  • 7 Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Münster, Germany; Munich Cluster for Systems Neurology (SyNergy), Münster, Germany. , (Germany)
  • 8 Department 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. , (Australia)
  • 9 Department 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. , (Germany)
  • 10 Division of Psychiatry, University of Edinburgh, Edinburgh, United Kingdom. , (United Kingdom)
  • 11 Department of Biological Psychology and EMGO+ Institute for Health and Care Research, Vrije Universiteit Medical Center, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. , (Netherlands)
  • 12 NIDO | Danmark, Regional Hospital West Jutland, Herning, Denmark; iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Denmark. , (Denmark)
  • 13 Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. , (Australia)
  • 14 Department of Psychiatry, University of Münster, Münster, Germany. , (Germany)
  • 15 Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands; Department of Psychiatry, Dokuz Eylul University School Of Medicine, Izmir, Turkey. , (Netherlands)
  • 16 Department 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.
  • 17 Institute 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. , (Switzerland)
  • 18 Department 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. , (Netherlands)
  • 19 Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany. , (Germany)
  • 20 Department of Psychiatry, Kaiser Permanente Northern California, San Francisco, California.
  • 21 Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, United Kingdom. , (United Kingdom)
  • 22 Department of Psychological Medicine, University of Worcester, Worcester, United Kingdom. , (United Kingdom)
  • 23 Psychiatry and the Behavioral Sciences, University of Southern California, Los Angeles, California.
  • 24 Institute of Social and Preventive Medicine, University Hospital of Lausanne, Lausanne, Switzerland; Swiss Institute of Bioinformatics, Lausanne, Switzerland. , (Switzerland)
  • 25 Psychiatry and Behavioral Sciences, Stanford University, Stanford, California.
  • 26 Division of Psychiatry, University College London, London, United Kingdom. , (United Kingdom)
  • 27 Max Planck Institute of Psychiatry, Munich, Germany. , (Germany)
  • 28 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. , (Sweden)
  • 29 Division of Psychiatry, University of Edinburgh, Edinburgh, United Kingdom; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom. , (United Kingdom)
  • 30 Department of Psychiatry, Amsterdam Universiteit Medical Center, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands. , (Netherlands)
  • 31 iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Denmark; Psychosis Research Unit, Aarhus University Hospital, Risskov, Aarhus, Denmark. , (Denmark)
  • 32 Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada; Department of Statistics, University of British Columbia, Vancouver, British Columbia, Canada. , (Canada)
  • 33 University 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. , (Germany)
  • 34 Psychiatry, University of Iowa, Iowa City, Iowa.
  • 35 Department of Psychiatry, University Hospital of Lausanne, Prilly, Switzerland. , (Switzerland)
  • 36 Analytic 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. , (Germany)
  • 37 Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
  • 38 Behavioral Health Services, Kaiser Permanente Washington, Seattle, Washington.
  • 39 Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. , (Germany)
  • 40 Department 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. , (Sweden)
  • 41 Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands; Child and Adolescent Psychiatry, Erasmus Medical Center, Rotterdam, The Netherlands; Psychiatry, Erasmus Medical Center, Rotterdam, The Netherlands. , (Netherlands)
  • 42 Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada. , (Canada)
  • 43 Division 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.
  • 44 Social 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. , (United Kingdom)
Type
Published Article
Publication Date
Mar 01, 2020
Volume
87
Issue
5
Pages
419–430
Identifiers
DOI: 10.1016/j.biopsych.2019.06.031
PMID: 31570195
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The 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. We 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 × 10-6) and a candidate threshold (1.6 × 10-4). No 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). We 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. Copyright © 2019 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

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