Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
QIMR Home Page
GenEpi Home Page
Publications
Contacts
Research
Staff Index
Collaborators
Software Tools
Computing Resources
Studies
Search
GenEpi Intranet
PMID
31570195
TITLE
Classical Human Leukocyte Antigen Alleles and C4 Haplotypes Are Not Significantly Associated With Depression.
ABSTRACT
BACKGROUND NlmCategory: BACKGROUND
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.
METHODS NlmCategory: METHODS
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 ) and a candidate threshold (1.6 × 10 ).
RESULTS NlmCategory: RESULTS
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 ) and a candidate threshold (1.6 × 10 ). 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).
CONCLUSIONS NlmCategory: CONCLUSIONS
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 ) and a candidate threshold (1.6 × 10 ). 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.
DATE PUBLISHED
2019 Aug 05
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2018/11/19
revised 2019/06/26
accepted 2019/06/27
entrez 2019/10/02 06:00
pubmed 2019/10/02 06:00
medline 2019/10/02 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Glanville KP Glanville Kylie P KP Social 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.
Coleman JRI Coleman Jonathan R I JRI 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.
Hanscombe KB Hanscombe Ken B KB Department of Medical and Molecular Genetics, King's College London, London, United Kingdom.
Euesden J Euesden Jack J Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
Choi SW Choi Shing Wan SW 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.
Purves KL Purves Kirstin L KL Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
Breen G Breen Gerome G 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.
Air TM Air Tracy M TM Discipline of Psychiatry, Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.
Andlauer TFM Andlauer Till F M TFM Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Münster, Germany; Munich Cluster for Systems Neurology (SyNergy), Münster, Germany.
Baune BT Baune Bernhard T BT 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.
Binder EB Binder Elisabeth B EB 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.
Blackwood DHR Blackwood Douglas H R DHR Division of Psychiatry, University of Edinburgh, Edinburgh, United Kingdom.
Boomsma DI Boomsma Dorret I DI Department of Biological Psychology and EMGO+ Institute for Health and Care Research, Vrije Universiteit Medical Center, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Buttenschøn HN Buttenschøn Henriette N HN NIDO | Danmark, Regional Hospital West Jutland, Herning, Denmark; iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Denmark.
Colodro-Conde L Colodro-Conde Lucía L Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Dannlowski U Dannlowski Udo U Department of Psychiatry, University of Münster, Münster, Germany.
Direk N Direk Nese N Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands; Department of Psychiatry, Dokuz Eylul University School Of Medicine, Izmir, Turkey.
Dunn EC Dunn Erin C EC 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.
Forstner AJ Forstner Andreas J AJ 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.
de Geus EJC de Geus Eco J C EJC 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.
Grabe HJ Grabe Hans J HJ Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
Hamilton SP Hamilton Steven P SP Department of Psychiatry, Kaiser Permanente Northern California, San Francisco, California.
Jones I Jones Ian I Medical Research Council Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, United Kingdom.
Jones LA Jones Lisa A LA Department of Psychological Medicine, University of Worcester, Worcester, United Kingdom.
Knowles JA Knowles James A JA Psychiatry and the Behavioral Sciences, University of Southern California, Los Angeles, California.
Kutalik Z Kutalik Zoltán Z Institute of Social and Preventive Medicine, University Hospital of Lausanne, Lausanne, Switzerland; Swiss Institute of Bioinformatics, Lausanne, Switzerland.
Levinson DF Levinson Douglas F DF Psychiatry and Behavioral Sciences, Stanford University, Stanford, California.
Lewis G Lewis Glyn G Division of Psychiatry, University College London, London, United Kingdom.
Lind PA Lind Penelope A PA Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Lucae S Lucae Susanne S Max Planck Institute of Psychiatry, Munich, Germany.
Magnusson PK Magnusson Patrik K PK Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
McGuffin P McGuffin Peter P Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
McIntosh AM McIntosh Andrew M AM Division of Psychiatry, University of Edinburgh, Edinburgh, United Kingdom; Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom.
Milaneschi Y Milaneschi Yuri Y Department of Psychiatry, Amsterdam Universiteit Medical Center, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Mors O Mors Ole O iPSYCH, The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Denmark; Psychosis Research Unit, Aarhus University Hospital, Risskov, Aarhus, Denmark.
Mostafavi S Mostafavi Sara S Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada; Department of Statistics, University of British Columbia, Vancouver, British Columbia, Canada.
Müller-Myhsok B Müller-Myhsok Bertram B 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.
Pedersen NL Pedersen Nancy L NL Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Penninx BWJH Penninx Brenda W J H BWJH Department of Psychiatry, Amsterdam Universiteit Medical Center, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Potash JB Potash James B JB Psychiatry, University of Iowa, Iowa City, Iowa.
Preisig M Preisig Martin M Department of Psychiatry, University Hospital of Lausanne, Prilly, Switzerland.
Ripke S Ripke Stephan S 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.
Shi J Shi Jianxin J Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland.
Shyn SI Shyn Stanley I SI Behavioral Health Services, Kaiser Permanente Washington, Seattle, Washington.
Smoller JW Smoller Jordan W JW 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.
Streit F Streit Fabian F Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Sullivan PF Sullivan Patrick F PF 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.
Tiemeier H Tiemeier Henning H Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands; Child and Adolescent Psychiatry, Erasmus Medical Center, Rotterdam, The Netherlands; Psychiatry, Erasmus Medical Center, Rotterdam, The Netherlands.
Uher R Uher Rudolf R Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada.
Van der Auwera S Van der Auwera Sandra S Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
Weissman MM Weissman Myrna M MM 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.
Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium
O'Reilly PF O'Reilly Paul F PF 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.
Lewis CM Lewis Cathryn M CM 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.
INVESTIGATORS
LASTNAME FORENAME INITIALS AFFILIATION
Wray Naomi R NR
Ripke Stephan S
Mattheisen Manuel M
Trzaskowski Maciej M
Byrne Enda M EM
Abdellaoui Abdel A
Adams Mark J MJ
Agerbo Esben E
Air Tracy M TM
Andlauer Till F M TFM
Bacanu Silviu-Alin SA
Bækvad-Hansen Marie M
Beekman Aartjan T F ATF
Bigdeli Tim B TB
Binder Elisabeth B EB
Bryois Julien J
Buttenschøn Henriette N HN
Bybjerg-Grauholm Jonas J
Cai Na N
Castelao Enrique E
Christensen Jane Hvarregaard JH
Clarke Toni-Kim TK
Coleman Jonathan R I JRI
Colodro-Conde Lucía L
Couvy-Duchesne Baptiste B
Craddock Nick N
Crawford Gregory E GE
Davies Gail G
Deary Ian J IJ
Degenhardt Franziska F
Derks Eske M EM
Direk Nese N
Dolan Conor V CV
Dunn Erin C EC
Eley Thalia C TC
Escott-Price Valentina V
Hassan Kiadeh Farnush Farhadi FF
Finucane Hilary K HK
Foo Jerome C JC
Forstner Andreas J AJ
Frank Josef J
Gaspar Héléna A HA
Gill Michael M
Goes Fernando S FS
Gordon Scott D SD
Grove Jakob J
Hall Lynsey S LS
Hansen Christine Søholm CS
Hansen Thomas F TF
Herms Stefan S
Hickie Ian B IB
Hoffmann Per P
Homuth Georg G
Horn Carsten C
Hottenga Jouke-Jan JJ
Hougaard David M DM
Howard David M DM
Ising Marcus M
Jansen Rick R
Jones Ian I
Jones Lisa A LA
Jorgenson Eric E
Knowles James A JA
Kohane Isaac S IS
Kraft Julia J
Kretzschmar Warren W WW
Kutalik Zoltán Z
Li Yihan Y
Lind Penelope A PA
MacIntyre Donald J DJ
MacKinnon Dean F DF
Maier Robert M RM
Maier Wolfgang W
Marchini Jonathan J
Mbarek Hamdi H
McGrath Patrick P
McGuffin Peter P
Medland Sarah E SE
Mehta Divya D
Middeldorp Christel M CM
Mihailov Evelin E
Milaneschi Yuri Y
Milani Lili L
Mondimore Francis M FM
Montgomery Grant W GW
Mostafavi Sara S
Mullins Niamh N
Nauck Matthias M
Ng Bernard B
Nivard Michel G MG
Nyholt Dale R DR
O'Reilly Paul F PF
Oskarsson Hogni H
Owen Michael J MJ
Painter Jodie N JN
Pedersen Carsten Bøcker CB
Pedersen Marianne Giørtz MG
Peterson Roseann E RE
Pettersson Erik E
Peyrot Wouter J WJ
Pistis Giorgio G
Posthuma Danielle D
Quiroz Jorge A JA
Qvist Per P
Rice John P JP
Riley Brien P BP
Rivera Margarita M
Mirza Saira Saeed SS
Schoevers Robert R
Schulte Eva C EC
Shen Ling L
Shi Jianxin J
Shyn Stanley I SI
Sigurdsson Engilbert E
Sinnamon Grant C B GCB
Smit Johannes H JH
Smith Daniel J DJ
Stefansson Hreinn H
Steinberg Stacy S
Streit Fabian F
Strohmaier Jana J
Tansey Katherine E KE
Teismann Henning H
Teumer Alexander A
Thompson Wesley W
Thomson Pippa A PA
Thorgeirsson Thorgeir E TE
Traylor Matthew M
Treutlein Jens J
Trubetskoy Vassily V
Uitterlinden Andrés G AG
Umbricht Daniel D
Van der Auwera Sandra S
van Hemert Albert M AM
Viktorin Alexander A
Visscher Peter M PM
Wang Yunpeng Y
Webb Bradley T BT
Weinsheimer Shantel Marie SM
Wellmann Jürgen J
Willemsen Gonneke G
Witt Stephanie H SH
Wu Yang Y
Xi Hualin S HS
Yang Jian J
Zhang Futao F
Arolt Volker V
Baune Bernhard T BT
Berger Klaus K
Boomsma Dorret I DI
Cichon Sven S
Dannlowski Udo U
de Geus E J C EJC
DePaulo J Raymond JR
Domenici Enrico E
Domschke Katharina K
Esko Tõnu T
Grabe Hans J HJ
Hamilton Steven P SP
Hayward Caroline C
Heath Andrew C AC
Kendler Kenneth S KS
Kloiber Stefan S
Lewis Glyn G
Li Qingqin S QS
Lucae Susanne S
Madden Pamela Af PA
Magnusson Patrik K PK
Martin Nicholas G NG
McIntosh Andrew M AM
Metspalu Andres A
Mors Ole O
Mortensen Preben Bo PB
Müller-Myhsok Bertram B
Nordentoft Merete M
Nöthen Markus M MM
O'Donovan Michael C MC
Paciga Sara A SA
Pedersen Nancy L NL
Penninx Brenda W J H BWJH
Perlis Roy H RH
Porteous David J DJ
Potash James B JB
Preisig Martin M
Rietschel Marcella M
Schaefer Catherine C
Schulze Thomas G TG
Smoller Jordan W JW
Stefansson Kari K
Tiemeier Henning H
Uher Rudolf R
Völzke Henry H
Weissman Myrna M MM
Werge Thomas T
Lewis Cathryn M CM
Levinson Douglas F DF
Breen Gerome G
Børglum Anders D AD
Sullivan Patrick F PF
JOURNAL
VOLUME:
ISSUE:
TITLE: Biological psychiatry
ISOABBREVIATION: Biol. Psychiatry
YEAR: 2019
MONTH: Aug
DAY: 05
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1873-2402
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Biol Psychiatry
COUNTRY: United States
ISSNLINKING: 0006-3223
NLMUNIQUEID: 0213264
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
COMMENTS AND CORRECTIONS
GRANTS
GENERAL NOTE
KEYWORDS
KEYWORD
Autoimmune disorder
Complement
Genetic association
Human leukocyte antigen
Major depressive disorder
Major histocompatibility complex
MESH HEADINGS
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's