Journal article

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

Kylie P Glanville, Jonathan R Coleman, Ken B Hanscombe, Jack Euesden, Shing Wan Choi, Kirstin L Purves, Gerome Breen, Tracy M Air, Till FM Andlauer, Bernhard T Baune, Elisabeth B Binder, Douglas HR Blackwood, Dorret Boomsma, Henriette N Buttenschon, Lucia Colodro-Conde, Udo Dannlowski, Nese Direk, Erin C Dunn, Andreas J Forstner, Eco JC de Geus Show all

Biological Psychiatry | ELSEVIER SCIENCE INC | Published : 2020

Abstract

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: 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 Bioban..

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University of Melbourne Researchers

Grants

Awarded by UK Medical Research Council


Awarded by Medical Research Council


Awarded by United States National Institute of Mental Health


Awarded by United States National Institute of Drug Abuse


Awarded by Netherlands Scientific Organization


Awarded by Deutsche Forschungsgemeinschaft, Germany


Awarded by German Federal Ministry for Education and Research (BMBF) IntegraMent, Germany


Awarded by BMBF NGFNplus MooDS, Germany


Awarded by National Health and Medical Research Council, Australia


Awarded by Lundbeck Foundation, Denmark


Awarded by Wellcome Trust, UK


Awarded by Medical Research Council, UK


Awarded by EU 6th framework, UK


Awarded by EU Innovative Medicines Initiative Joint Undertaking, UK


Awarded by National Institute of Mental Health (NIMH)


Awarded by BMBF in the National Genome Research Network framework (NGFN2)


Awarded by BMBF in the National Genome Research Network framework (NGFN-Plus)


Awarded by BMBF


Awarded by Geestkracht program of the Netherlands Organization for Health Research and Development (ZonMw)


Awarded by Netherlands Organization for Scientific Research (NOW)


Awarded by Biobanking and Biomolecular Resources Research Infrastructure


Awarded by National Institutes of Health (Genetic Association Information Network [GAIN] of the Foundation for the National Institutes of Health)


Awarded by Swiss National Science Foundation, Switzerland


Awarded by National Institute on Alcohol Abuse and Alcoholism


Awarded by NIMH, UK


Awarded by Netherlands Organization of Scientific Research (NWO)


Awarded by Federal Ministry of Education and Research


Awarded by German Research Foundation


Awarded by NIMH


Awarded by GenomeEUtwin, EU


Awarded by Heart and Lung foundation, Sweden


Awarded by Vetenskapsradet, Sweden


Awarded by Guy's and St Thomas' Charity


Awarded by Maudsley Charity


Awarded by Hojteknologifonden, Denmark


Funding Acknowledgements

62 This work was supported by the UK Medical Research Council (Grant No. MR/N015746/1 Grant No. MR/N015746/1, Ph.D. studentship [to KPG]) and partially funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley National Health Service (NHS) Foundation Trust and King's College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care.We thank participants and scientists involved in making the UK Biobank resource available (http://www.ukbiobank.ac.uk/).UK Biobank data used in this study were obtained under approved application 18177, which was supported by funding from the Medical Research Council (Grant No. MR/N015746/1).We are deeply indebted to the investigators who comprise the PGC and to the hundreds of thousands of participants who have shared their life experiences with PGC investigators. The PGC has received major funding from the United States National Institute of Mental Health (Grant No. U01 MH109528-03 [principal investigator, P.F. Sullivan]), the United States National Institute of Drug Abuse (Grant No. U01 MH1095320 [principal investigator A. Agrawal]), the Netherlands Scientific Organization (Grant No. 480-05-003 [principal investigator, D. Posthuma]), and the Dutch Brain Foundation and the Vrije Universiteit Amsterdam (principal investigator, D. Posthuma).BOMA: Funding support was provided by Deutsche Forschungsgemeinschaft, Germany (Grant Nos. RI 908/11-1, NO246/10-1 and Excellence Cluster ImmunoSensation [principal investigators, M. Rietschel and M.M. Nothen]), the German Federal Ministry for Education and Research (BMBF) IntegraMent, Germany (Grant Nos. 01ZX1314A/01ZX1614A and 01ZX1314G/01ZX1614G [principal investigators, M.M. Nothen, M. Rietschel, and S. Cichon]), and BMBF NGFNplus MooDS, Germany (Grant Nos. 01GS08144 and 01GS08147 [principal investigators, M.M. Nothen, M. Rietschel, and S. Cichon]).CoFaMS - Adelaide: Funding support was provided by National Health and Medical Research Council, Australia (Grant No. APP1060524 [principal investigator, B.T. Baune]).Danish Radiant: Funding support was provided by Hojteknologifonden, Denmark (Grant No. 0001-2009-2 [principal investigators, T. Werge (controls) and O. Mors (cases)]) and Lundbeck Foundation, Denmark (Grant No. R24-A3242 [principal investigators, T. Werge (controls) and O. Mors (cases)])EDINBURGH: Genotyping was conducted at the Genetics Core Laboratory at the Clinical Research Facility (University of Edinburgh). Funding support was provided by Wellcome Trust, UK (Grant No. 104036/Z/14/Z [principal investigator, A.M. McIntosh]).GenPod/Newmeds: Funding support was provided by the Medical Research Council, UK (Grant No. G0200243 [principal investigators, G. Lewis and M. O'Donovan]), EU 6th framework, UK (Grant No. LSHB-CT-2003-503428 [principal investigator, R. Uher]), and EU Innovative Medicines Initiative Joint Undertaking, UK (Grant No. 15008 [principal investigator, G. Lewis]).GSK-MUNICH: We thank all participants in the GSK-Munich study. We thank numerous people at GSK and Max Planck Institute, BKH Augsburg, and Klinikum Ingolstadt in Germany who contributed to this project.Harvard i2b2: Funding support was provided by the National Institute of Mental Health (NIMH) (Grant Nos. R01 MH085542 and R01 MH086026 [principal investigators, J.W. Smoller and R.H. Perlis])MARS: This work was funded by the Max Planck Society, the Max Planck Excellence Foundation, the BMBF in the National Genome Research Network framework (NGFN2 and NGFN-Plus) (Grant No. FKZ 01GS0481), and by the BMBF Program (Grant No. FKZ 01ES0811). We acknowledge all study participants. We thank numerous people at Max Planck Institute, and all study sites in Germany and Switzerland who contributed to this project. Controls were from the Dortmund Health Study, which was supported NGFNplus MooDS by the German Migraine and Headache Society and by unrestricted grants to the University of Munster from Almirall, AstraZeneca, Berlin Chemie, Boehringer, Boots Health Care, Glaxo-Smith-Kline, Janssen Cilag, McNeil Pharma, MSD Sharp and Dohme, and Pfizer. Blood collection was funded by the Institute of Epidemiology and Social Medicine, University of Munster. Genotyping was supported by the BMBF (Grant No. 01ER0816).NESDA: The infrastructure for the NESDA study (www.nesda.nl) is funded through the Geestkracht program of the Netherlands Organization for Health Research and Development (ZonMw) (Grant No. 10-000-1002) and financial contributions by participating universities and mental health care organizations (Vrije Universiteit Medical Center, GGZ inGeest, Leiden University Medical Center, Leiden University, GGZ Rivierduinen, University Medical Center Groningen, University of Groningen, Lentis, GGZ Friesland, GGZ Drenthe, and Rob Giel Onderzoekscentrum). Genotyping was supported by the Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL) and National Institutes of Health (Genetic Association Information Network [GAIN] of the Foundation for the National Institutes of Health, Grand Opportunity Grnat Nos. 1RC2 MH089951 and 1RC2 MH089995 [principal investigator, BJWH Penninx]).NTR: NTR is supported by the Netherlands Organization for Scientific Research (NOW) (Grant No. 480-15-001/674)BBMRI-NL: Funding support was provided by Biobanking and Biomolecular Resources Research Infrastructure (Grant Nos. 184.021.007 and BBMRI-NL2.0 184.033.111). Genotyping was supported by BBMRI-NL, the Avera Institute, Sioux Falls, SD, and National Institutes of Health (Genetic Association Information Network [GAIN] of the Foundation for the National Institutes of Health, Grand Opportunity Grant Nos. 1RC2 MH089951 and 1RC2 MH089995 [principal investigator, D.I. Boomsma]).PsyColaus: Funding support was provided by the Swiss National Science Foundation, Switzerland (Grant Nos. 3200B0-105993, 3200B0118308, 33CSCO-122661, 33CS30-139468, and 33CS30-148401 [principal investigator, M. Preisig]). PsyCoLaus/CoLaus received additional support from research grants from GlaxoSmithKline and the Faculty of Biology and Medicine of Lausanne.QIMR: We thank the twins and their families for their willing participation in our studies. Funding support was provided by the National Health and Medical Research Council, Australia (Grant Nos. 941177, 971232, 3399450, and 443011 [principal investigator, N.G. Martin]) and National Institute on Alcohol Abuse and Alcoholism (Grant Nos. AA07535, AA07728, and AA10249 [principal investigator, A.C. Heath]).RADIANT: This report represents independent research funded by the NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust, and King's College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health. Funding support was provided by the Medical Research Council, UK (Grant Nos. G0701420 and G0901245 [principal investigators, C. Lewis and G. Breen]) and NIMH, UK (Grant No. U01 MH109528 [principal investigator, G. Breen]).Rotterdam Study: Funding support was provided by the Netherlands Organization of Scientific Research (NWO) Investments (Grant No. 175.010.2005.011, 911-03-012 [principal investigator, A.G. Uitterlinden]). The Rotterdam Study is also funded by Erasmus Medical Center and Erasmus University.SHIP-LEGEND/TREND: SHIP is part of the Community Medicine Research net of the University of Greifswald, which is funded by the Federal Ministry of Education and Research (Grant Nos. 01ZZ9603, 01ZZ0103, and 01ZZ0403), the Ministry of Cultural Affairs, and the Social Ministry of the Federal State of Mecklenburg-West Pomerania. Genotyping in SHIP was funded by Siemens Healthineers and the Federal State of MecklenburgWest Pomerania. The SHIP-LEGEND/TREND Study is also funded by the German Research Foundation (Grant No. DFG: GR 1912/5-1 [principal investigator, H.J. Grabe]). Genotyping in SHIP-TREND-0 was supported by the Federal Ministry of Education and Research (Grant No. 03ZIK012).STAR*D: The authors appreciate the efforts of the STAR*D investigator team for acquiring, compiling, and sharing the STAR*D clinical data set. Funding support was provided by NIMH (Grant No. R01 MH-072802 [principal investigator, S.P. Hamilton]).TwinGene: Thanks the Karolinska Institutet for infrastructural support of the Swedish Twin Registry. Funding support was provided by GenomeEUtwin, EU (Grant Nos. EU/QLRT-2001-01254 and QLG2-CT-2002-01254 [principal investigator, N. Pedersen]), the Heart and Lung foundation, Sweden (Grant No. 20070481 [principal investigator, P. Magnusson]), SSF, Sweden and Vetenskapsradet, Sweden (Grant No. M-2005-1112 [principal investigator, U. de Faire]).Funding support for the Genome-Wide Association of Schizophrenia Study was provided by NIMH (Grant Nos. R01 MH67257, R01 MH59588, R01 MH59571, R01 MH59565, R01 MH59587, R01 MH60870, R01 MH59566, R01 MH59586, R01 MH61675, R01 MH60879, R01 MH81800,U01 MH46276, U01 MH46289 U01 MH46318, U01 MH79469, and U01 MH79470), and the genotyping of samples was provided through GAIN. The data sets used for the analyses described in this manuscript were obtained from the database of Genotypes and Phenotypes (dbGaP) found at http://www.ncbi.nlm.nih.gov/gap through dbGaP accession number phs000021.v3.p2. Samples and associated phenotype data for the Genome-Wide Association of Schizophrenia Study were provided by the Molecular Genetics of Schizophrenia Collaboration (principal investigator, Pablo V. Gejman, Evanston Northwestern Healthcare (ENH) and Northwestern University, Evanston, IL).Statistical analyses were performed on the NL Genetic Cluster computer (http://www.geneticcluster.org/) hosted by SURFsara, and the King's Health Partners High Performance Compute Cluster funded with capital equipment grants from the Guy's and St Thomas' Charity (Grant No. TR130505) and Maudsley Charity (Grant No. 980).