Nature Communications (Feb 2025)
Insights from a methylome-wide association study of antidepressant exposure
- E. Davyson,
- X. Shen,
- F. Huider,
- M. J. Adams,
- K. Borges,
- D. L. McCartney,
- L. F. Barker,
- J. van Dongen,
- D. I. Boomsma,
- A. Weihs,
- H. J. Grabe,
- L. Kühn,
- A. Teumer,
- H. Völzke,
- T. Zhu,
- J. Kaprio,
- M. Ollikainen,
- F. S. David,
- S. Meinert,
- F. Stein,
- A. J. Forstner,
- U. Dannlowski,
- T. Kircher,
- A. Tapuc,
- D. Czamara,
- E. B. Binder,
- T. Brückl,
- A. S. F. Kwong,
- P. Yousefi,
- C. C. Y. Wong,
- L. Arseneault,
- H. L. Fisher,
- J. Mill,
- S. R. Cox,
- P. Redmond,
- T. C. Russ,
- E. J. C. G. van den Oord,
- K. A. Aberg,
- B. W. J. H. Penninx,
- R. E. Marioni,
- N. R. Wray,
- A. M. McIntosh
Affiliations
- E. Davyson
- Division of Psychiatry, Centre for Clinical Brain Sciences, University of Edinburgh
- X. Shen
- Division of Psychiatry, Centre for Clinical Brain Sciences, University of Edinburgh
- F. Huider
- Complex Trait Genetics, Center of Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam
- M. J. Adams
- Division of Psychiatry, Centre for Clinical Brain Sciences, University of Edinburgh
- K. Borges
- Division of Psychiatry, Centre for Clinical Brain Sciences, University of Edinburgh
- D. L. McCartney
- Institute of Genetics and Cancer, University of Edinburgh
- L. F. Barker
- Institute for Molecular Bioscience, University of Queensland
- J. van Dongen
- Complex Trait Genetics, Center of Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam
- D. I. Boomsma
- Complex Trait Genetics, Center of Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam
- A. Weihs
- Department of Psychiatry and Psychotherapy, University Medicine Greifswald
- H. J. Grabe
- Department of Psychiatry and Psychotherapy, University Medicine Greifswald
- L. Kühn
- Department of Psychiatry and Psychotherapy, University Medicine Greifswald
- A. Teumer
- Department of Psychiatry and Psychotherapy, University Medicine Greifswald
- H. Völzke
- German Centre for Cardiovascular Research (DZHK), Partner Site Greifswald
- T. Zhu
- Institute for Molecular Medicine Finland FIMM, HiLIFE, University of Helsinki
- J. Kaprio
- Institute for Molecular Medicine Finland FIMM, HiLIFE, University of Helsinki
- M. Ollikainen
- Institute for Molecular Medicine Finland FIMM, HiLIFE, University of Helsinki
- F. S. David
- Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn
- S. Meinert
- Institute for Translational Psychiatry, University of Münster
- F. Stein
- Department of Psychiatry and Psychotherapy, University of Marburg
- A. J. Forstner
- Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn
- U. Dannlowski
- Institute for Translational Psychiatry, University of Münster
- T. Kircher
- Department of Psychiatry and Psychotherapy, University of Marburg
- A. Tapuc
- Max Planck School of Cognition
- D. Czamara
- Max-Planck-Institute of Psychiatry, Department Genes and Environment
- E. B. Binder
- Max-Planck-Institute of Psychiatry, Department Genes and Environment
- T. Brückl
- Max-Planck-Institute of Psychiatry, Department Genes and Environment
- A. S. F. Kwong
- Division of Psychiatry, Centre for Clinical Brain Sciences, University of Edinburgh
- P. Yousefi
- Medical Research Council Integrative Epidemiology Unit at the University of Bristol, University of Bristol
- C. C. Y. Wong
- Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London
- L. Arseneault
- Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London
- H. L. Fisher
- Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London
- J. Mill
- Department of Clinical & Biomedical Sciences, University of Exeter Medical School, University of Exeter
- S. R. Cox
- Lothian Birth Cohorts, Department of Psychology, University of Edinburgh
- P. Redmond
- Lothian Birth Cohorts, Department of Psychology, University of Edinburgh
- T. C. Russ
- Division of Psychiatry, Centre for Clinical Brain Sciences, University of Edinburgh
- E. J. C. G. van den Oord
- Center for Biomarker Research and Precision Medicine (BPM), Virginia Commonwealth University
- K. A. Aberg
- Center for Biomarker Research and Precision Medicine (BPM), Virginia Commonwealth University
- B. W. J. H. Penninx
- Department of Psychiatry, Amsterdam UMC, Vrije Universiteit Amsterdam
- R. E. Marioni
- Institute of Genetics and Cancer, University of Edinburgh
- N. R. Wray
- Institute for Molecular Bioscience, University of Queensland
- A. M. McIntosh
- Division of Psychiatry, Centre for Clinical Brain Sciences, University of Edinburgh
- DOI
- https://doi.org/10.1038/s41467-024-55356-x
- Journal volume & issue
-
Vol. 16,
no. 1
pp. 1 – 15
Abstract
Abstract 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.
