ArticleNature. Mental health2025
A methylome-wide association study of major depression with out-of-sample case-control classification and trans-ancestry comparison.
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Article in Nature. Mental health, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
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9citing papers in PubMed, 1 pooled it
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Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Epigenetic and blood markers associated with response to electroconvulsive therapy in patients with depressive disorders.Translational psychiatry · 2025Pooled it
- Effects of 6-months of SSRI use on DNA-methylation and gene expression in blood.Brain, behavior, and immunity · 2026Trial
- Epigenetic dysregulation in depression: molecular mechanisms, clinical biomarkers, and therapeutic opportunities.Journal of translational medicine · 2026Review
- DNA methylation signatures associated with bipolar disorder in peripheral blood improve prediction models.EBioMedicine · 2026Article
- Precision medicine in mental health: applications, challenges, and recommendations.European psychiatry : the journal of the Association of European Psychiatrists · 2026Review
- UK Household Longitudinal Study: cohort profile.BMJ medicine · 2026Article
- Epigenetic and genetic profiling of comorbidity patterns among substance dependence diagnoses.Molecular psychiatry · 2025Article
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Authors and funding
80 authors.
Xueyi ShenInstitute of Neuroscience and Cardiovascular Research, University of Edinburgh, Edinburgh, UK.ORCID 0000-0002-0538-4774
Miruna BarbuInstitute of Neuroscience and Cardiovascular Research, University of Edinburgh, Edinburgh, UK.
Doretta CaramaschiFaculty of Health and Life Sciences, Department of Psychology, University of Exeter, Exeter, UK.ORCID 0000-0002-9740-871X
Ryan ArathimosSocial, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Darina CzamaraDepartment Genes and Environment, Max-Planck-Institute of Psychiatry, Munich, Germany.ORCID 0000-0001-7381-904X
Friederike S DavidInstitute of Human Genetics, University of Bonn, School of Medicine and University Hospital Bonn, Bonn, Germany.ORCID 0000-0001-9521-5669
Anna DearmanInstitute for Social and Economic Research, University of Essex, Colchester, UK.ORCID 0000-0001-9385-2015
Evelyn DilkesInstitute for Social and Economic Research, University of Essex, Colchester, UK.
Marisol Herrera-RiveroDepartment of Genetic Epidemiology, Institute of Human Genetics, University of Münster, Münster, Germany.ORCID 0000-0001-7064-9487
Floris HuiderBiological Psychology, Amsterdam Public Health Institute, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.ORCID 0000-0001-7776-7988
Luise KühnDepartment of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.ORCID 0000-0002-0158-8286
Kuan-Chen LuInstitute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan.
Teemu PalviainenInstitute for Molecular Medicine Finland-FIMM, University of Helsinki, Helsinki, Finland.ORCID 0000-0002-7847-8384
Alicia M SchoweDepartment Genes and Environment, Max-Planck-Institute of Psychiatry, Munich, Germany.
Gemma ShirebyUniversity of Exeter Medical School, University of Exeter, Exeter, UK.
Antoine WeihsDepartment of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.ORCID 0000-0002-7113-0027
Chloe C Y WongSocial, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Eleanor DavysonSchool of Informatics, University of Edinburgh, Edinburgh, UK.ORCID 0000-0002-7313-0530
Hannah CaseyInstitute of Neuroscience and Cardiovascular Research, University of Edinburgh, Edinburgh, UK.
Mark J AdamsInstitute of Neuroscience and Cardiovascular Research, University of Edinburgh, Edinburgh, UK.ORCID 0000-0002-3599-6018
Antje-Kathrin AllgaierDepartment of Human Sciences, University of the Bundeswehr Munich, Munich, Germany.
Michael BarberMRC Human Genetics Unit, University of Edinburgh, Edinburgh, UK.
Joe BurrageDepartment of Clinical and Biomedical Sciences, University of Exeter, Exeter, UK.
Avshalom CaspiSocial, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.ORCID 0000-0003-0082-4600
Ricardo CosteiraDepartment of Twin Research and Genetic Epidemiology, King's College London, London, UK.
Erin C DunnPsychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA USA.ORCID 0000-0003-1413-3229
Lisa FeldmannDepartment of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, LMU University Hospital, Ludwig-Maximilians-University (LMU) Munich, Munich, Germany.
Josef FrankDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.ORCID 0000-0003-4867-9465
Franz J Freislederkbo-Heckscher-Klinikum gGmbH, Munich, Germany.
Danni A GaddInstitute of Genetics and Cancer, Centre for Genomic and Experimental Medicine, University of Edinburgh, Edinburgh, UK.
Ellen GreimelDepartment of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, LMU University Hospital, Ludwig-Maximilians-University (LMU) Munich, Munich, Germany.ORCID 0000-0002-9916-9230
Eilis HannonDepartment of Clinical and Biomedical Sciences, University of Exeter, Exeter, UK.
Sarah E HarrisLothian Birth Cohorts group, Department of Psychology, University of Edinburgh, Edinburgh, UK.ORCID 0000-0002-4941-5106
Georg HomuthInterfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.ORCID 0000-0001-6839-0605
David M HowardSocial, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.ORCID 0000-0002-6005-1972
Stella IuratoDepartment Genes and Environment, Max-Planck-Institute of Psychiatry, Munich, Germany.
Tellervo KorhonenInstitute for Molecular Medicine Finland-FIMM, University of Helsinki, Helsinki, Finland.
Tzu-Pin LuDepartment of Public Health and Institute of Health Data Analytics and Statistics, National Taiwan University, Taipei, Taiwan.
Nicholas G MartinQueensland Institute of Medical Research Berghofer, Brisbane, Queensland Australia.ORCID 0000-0003-4069-8020
Jade MartinsDecision Intelligence, Knorr-Bremse Services GmbH, Munich, Germany.
Edel McDermottCentre for Colorectal Disease, St Vincent's University Hospital, Dublin, Ireland.
Susanne MeinertInstitute for Translational Psychiatry, University of Münster, Münster, Germany.ORCID 0000-0003-2177-7161
Pau NavarroMRC Human Genetics Unit, University of Edinburgh, Edinburgh, UK.ORCID 0000-0001-5576-8584
Miina OllikainenInstitute for Molecular Medicine Finland-FIMM, University of Helsinki, Helsinki, Finland.
Verena PehlDepartment of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, LMU University Hospital, Ludwig-Maximilians-University (LMU) Munich, Munich, Germany.
Charlotte PiechaczekDepartment of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, LMU University Hospital, Ludwig-Maximilians-University (LMU) Munich, Munich, Germany.
Aline D ScherffDepartment of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, LMU University Hospital, Ludwig-Maximilians-University (LMU) Munich, Munich, Germany.ORCID 0000-0002-7420-2292
Frederike SteinDepartment of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany.ORCID 0000-0002-5052-6022
Fabian StreitDepartment of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.ORCID 0000-0003-1080-4339
Alexander TeumerDepartment of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.ORCID 0000-0002-8309-094X
Henry VölzkeGerman Centre for Cardiovascular Research (DZHK), Greifswald, Germany.
Jenny van DongenBiological Psychology, Amsterdam Public Health Institute, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
Rosie M WalkerFaculty of Health and Life Sciences, Department of Psychology, University of Exeter, Exeter, UK.
Natan YusupovDepartment Genes and Environment, Max-Planck-Institute of Psychiatry, Munich, Germany.
Louise ArseneaultSocial, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.ORCID 0000-0002-2938-2191
Jordana T BellDepartment of Twin Research and Genetic Epidemiology, King's College London, London, UK.
Klaus BergerInstitute of Epidemiology and Social Medicine, University of Münster, Münster, Germany.
Elisabeth BinderDepartment Genes and Environment, Max-Planck-Institute of Psychiatry, Munich, Germany.
Dorret I BoomsmaComplex Trait Genetics, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.ORCID 0000-0002-7099-7972
Simon R CoxLothian Birth Cohorts group, Department of Psychology, University of Edinburgh, Edinburgh, UK.ORCID 0000-0003-4036-3642
Udo DannlowskiInstitute for Translational Psychiatry, University of Münster, Münster, Germany.ORCID 0000-0002-0623-3759
Kathryn L EvansInstitute for Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
Helen L FisherSocial, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.ORCID 0000-0003-4174-2126
Andreas J ForstnerInstitute of Human Genetics, University of Bonn, School of Medicine and University Hospital Bonn, Bonn, Germany.
Hans J GrabeDepartment of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
Jaakko KaprioInstitute for Molecular Medicine Finland-FIMM, University of Helsinki, Helsinki, Finland.
Tilo KircherDepartment of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany.ORCID 0000-0002-2514-2625
Johannes Kopf-BeckClinical Department, Max Planck Institute of Psychiatry, Munich, Germany.ORCID 0000-0002-0368-3930
Meena KumariInstitute for Social and Economic Research, University of Essex, Colchester, UK.
Po-Hsiu KuoDepartment of Public Health & Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan.
Qingqin S LiNeuroscience, Janssen Research and Development, Titusville, NJ USA.
Terrie E MoffittSocial, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Hugh MulcahyCentre for Colorectal Disease, St Vincent's University Hospital, Dublin, Ireland.
Therese M MurphySchool of Biological, Health and Sports Sciences, Technological University Dublin, Dublin, Ireland.ORCID 0000-0002-7647-2798
Gerd Schulte-KörneDepartment of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, LMU University Hospital, Ludwig-Maximilians-University (LMU) Munich, Munich, Germany.
Jonathan MillUniversity of Exeter Medical School, University of Exeter, Exeter, UK.
Cathryn M LewisSocial, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.ORCID 0000-0002-8249-8476
PGC MDD Working Group
Naomi R WrayInstitute for Molecular Bioscience, University of Queensland, Brisbane, Queensland Australia.ORCID 0000-0001-7421-3357
Andrew M McIntoshInstitute of Neuroscience and Cardiovascular Research, University of Edinburgh, Edinburgh, UK.ORCID 0000-0002-0198-4588
Funding
The development of alcohol misuse and related problems from adolescence to early midlifeR01AA015416 · NIAAA · WASHINGTON UNIVERSITY · PI DICK, DANIELLE M, SALVATORE, JESSICA E · 2005 to 2024
$7.6MTwin, molecular, and developmental approaches to understanding alcohol misuseK02AA018755 · NIAAA · VIRGINIA COMMONWEALTH UNIVERSITY · PI DICK, DANIELLE M · 2010 to 2019
$1.3MAdolescent Alcohol Abuse: A Twin-Study PerspectiveR01AA012502 · NIAAA · TRUSTEES OF INDIANA UNIVERSITY · PI ROSE, RICHARD JOSEPH · 2013 to 2017
$1.2MALCOHOL INTAKE DURING PREGNANCY: OFFSPRING DEVELOPMENTR01AA001455 · NIAAA · UNIVERSITY OF WASHINGTON · PI STREISSGUTH, ANN P · 1985 to 1998
–NIAAA NIH HHS K02 AA018755NIAAA NIH HHS R01 AA001455NIAAA NIH HHS R01 AA012502NIAAA NIH HHS R01 AA015416
Abstract
Major depression (MD) is a leading cause of global disease burden, and both experimental and population-based studies suggest that differences in DNA methylation may be associated with the condition. However, previous DNA methylation studies have, so far, not been widely replicated, suggesting a need for larger meta-analysis studies. Here we conducted a meta-analysis of methylome-wide association analysis for lifetime MD across 18 studies of 24,754 European-ancestry participants (5,443 MD cases) and an East Asian sample (243 cases, 1,846 controls). We identified 15 CpG sites associated with lifetime MD with methylome-wide significance. The methylation score created using the methylome-wide association analysis summary statistics was significantly associated with MD status in an out-of-sample classification analysis (area under the curve 0.53). Methylation score was also associated with five inflammatory markers, with the strongest association found with tumor necrosis factor beta. Mendelian randomization analysis revealed 23 CpG sites potentially causally linked to MD, with 7 replicated in an independent dataset. Our study provides evidence that variations in DNA methylation are associated with MD, and further evidence supporting involvement of the immune system.
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DepressionDNA methylationEpigenomicsPredictive markers
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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.