Insights from a methylome-wide association study of antidepressant exposure
This study tests the association of whole-blood DNA methylation and antidepressant exposure in 16,531 individuals from Generation Scotland (GS), using self-report and prescription-derived measures. We identify 8 associations and a high concordance of results between self-report and prescription-derived measures. Sex-stratified analyses observe nominally significant increased effect estimates in females for four CpGs. There is observed enrichment for genes expressed in the Amygdala and annotated to synaptic vesicle membrane ontology. Two CpGs (cg15071067; DGUOK-AS1 and cg26277237; KANK1) show correlation between DNA methylation with the time in treatment. There is a significant overlap in the top 1% of CpGs with another independent methylome-wide association study of antidepressant exposure. Finally, a methylation profile score trained on this sample shows a significant association with antidepressant exposure in a meta-analysis of eight independent external datasets. In this large investigation of antidepressant exposure and DNA methylation, we demonstrate robust associations which warrant further investigation to inform on the design of more effective and tolerated treatments for depression.
Authors
- Louise Arseneault (ORCID: https://orcid.org/0000-0002-2938-2191)
- Antoine Weihs (ORCID: https://orcid.org/0000-0002-7113-0027)
- Jaakko A. Kaprio (ORCID: https://orcid.org/0000-0002-3716-2455)
- Karin Borges (ORCID: https://orcid.org/0000-0001-7448-0770)
- Helen L. Fisher (ORCID: https://orcid.org/0000-0003-4174-2126)
- Andrew Mark McIntosh (ORCID: https://orcid.org/0000-0002-0198-4588)
- Henry Völzke (ORCID: https://orcid.org/0000-0001-7003-399X)
- Elisabeth B. Binder (ORCID: https://orcid.org/0000-0001-7088-6618)
- Edwin J. C. G. van den Oord (ORCID: https://orcid.org/0000-0003-2701-4405)
- Darina Czamara (ORCID: https://orcid.org/0000-0001-7381-904X)
- Lindsey Barker (ORCID: https://orcid.org/0000-0003-3356-5625)
- Susanne L. Meinert (ORCID: https://orcid.org/0000-0003-2177-7161)
- Paul Yousefi (ORCID: https://orcid.org/0000-0003-3284-3240)
- Hans Jörgen Grabe (ORCID: https://orcid.org/0000-0003-3684-4208)
- Daniel L. McCartney (ORCID: https://orcid.org/0000-0003-3242-0360)
- Miina Ollikainen (ORCID: https://orcid.org/0000-0003-3661-7400)
- Xueyi Shen (ORCID: https://orcid.org/0000-0002-0538-4774)
- Floris Huider (ORCID: https://orcid.org/0000-0001-7776-7988)
- Andreas J. Forstner (ORCID: https://orcid.org/0000-0002-1876-6368)
- Tom C. Russ (ORCID: https://orcid.org/0000-0001-9797-2188)
- Jonathan S. Mill (ORCID: https://orcid.org/0000-0003-1115-3224)
- Karolina A. Åberg (ORCID: https://orcid.org/0000-0001-6103-5168)
- Brenda W.J.H. Penninx (ORCID: https://orcid.org/0000-0001-7779-9672)
- Annemarie Luise Kühn (ORCID: https://orcid.org/0000-0002-0158-8286)
- Tanja Brückl (ORCID: https://orcid.org/0000-0003-2952-6375)
- Tianyu Zhu (ORCID: https://orcid.org/0000-0002-4781-7398)
- Chloe C. Y. Wong (ORCID: https://orcid.org/0000-0003-4886-8506)
- Frederike Stein (ORCID: https://orcid.org/0000-0002-5052-6022)
- Alex S. F. Kwong (ORCID: https://orcid.org/0000-0003-1953-2771)
- Naomi R. Wray (ORCID: https://orcid.org/0000-0001-7421-3357)
- Paul H. Redmond (ORCID: https://orcid.org/0000-0001-8272-8596)
- Riccardo E. Marioni (ORCID: https://orcid.org/0000-0003-4430-4260)
- Udo Dannlowski (ORCID: https://orcid.org/0000-0002-0623-3759)
- Tilo T. J. Kircher (ORCID: https://orcid.org/0000-0002-2514-2625)
- Eleanor Davyson (ORCID: https://orcid.org/0000-0002-7313-0530)
- Simon R. Cox (ORCID: https://orcid.org/0000-0003-4036-3642)
- Friederike Sophie David (ORCID: https://orcid.org/0000-0001-9521-5669)
- Jenny van Dongen (ORCID: https://orcid.org/0000-0003-2063-8741)
- Dorret Irene Boomsma (ORCID: https://orcid.org/0000-0002-7099-7972)
- Alexander Teumer (ORCID: https://orcid.org/0000-0002-8309-094X)
- Mark J. Adams (ORCID: https://orcid.org/0000-0002-3599-6018)
- A. Tapuc
Institutions
- NHS Lothian (GB)
- University of Helsinki (FI)
- University of Bonn (DE)
- Philipps University of Marburg (DE)
- The University of Queensland (AU)
- Forschungszentrum Jülich (DE)
- King's College London (GB)
- Virginia Commonwealth University (US)
- University of Münster (DE)
- University of Exeter (GB)
- Universitätsmedizin Greifswald (DE)
- University Hospital Bonn (DE)
- University Hospitals Bristol NHS Foundation Trust (GB)
- German Center for Neurodegenerative Diseases (DE)
- Edinburgh Cancer Research (GB)
- University of Bristol (GB)
- University of Oxford (GB)
- Alzheimer Scotland (GB)
- Minerva Foundation (FI)
- Brain (Germany) (DE)
- NIHR Bristol Biomedical Research Centre (GB)
- German Centre for Cardiovascular Research (DE)
- Max Planck Institute for Human Cognitive and Brain Sciences (DE)
- Institute for Molecular Medicine Finland (FI)
- Max Planck Institute of Psychiatry (DE)
- Amsterdam University Medical Centers (NL)
- Vrije Universiteit Amsterdam (NL)
- Medical Research Council (GB)
- University of Edinburgh (GB)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-02-24
- DOI
- https://doi.org/10.1038/s41467-024-55356-x
- Citations
- 6
- Primary Topic
- Epigenetics and DNA Methylation
- Type
- article
- Field-Weighted Citation Impact
- 4.84
Funders
- South London and Maudsley NHS Foundation Trust
- Wellcome Trust
- Deutsches Zentrum für Herz-Kreislaufforschung
- Broad Institute
- UK Research and Innovation
- National Institute for Health and Care Research
- Department of Health and Social Care
- Age UK
- King's College London
- European Commission
- University of Bristol
- Deutsche Forschungsgemeinschaft
- Universiteit Leiden
- Koninklijke Nederlandse Akademie van Wetenschappen
- Vrije Universiteit Amsterdam
- Bundesministerium für Bildung und Forschung
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- Max-Planck-Gesellschaft
- Leids Universitair Medisch Centrum
- Universitair Medisch Centrum Groningen
- Universität Greifswald
- Ministry of Cultural Affairs
- National Institutes of Health
- Directorate for Biological Sciences
- NIHR Maudsley Biomedical Research Centre
- Medical Research Council
- Economic and Social Research Council
- National Health and Medical Research Council
- National Heart, Lung, and Blood Institute
- National Institute of Mental Health
- FP7 Health