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Insights from a methylome-wide association study of antidepressant exposure

Author

Listed:
  • E. Davyson

    (University of Edinburgh
    University of Edinburgh)

  • X. Shen

    (University of Edinburgh)

  • F. Huider

    (Vrije Universiteit Amsterdam
    Amsterdam Public Health Research Institute
    Vrije Universiteit Amsterdam)

  • M. J. Adams

    (University of Edinburgh)

  • K. Borges

    (University of Edinburgh)

  • D. L. McCartney

    (University of Edinburgh)

  • L. F. Barker

    (University of Queensland)

  • J. Dongen

    (Vrije Universiteit Amsterdam
    Amsterdam Public Health Research Institute
    Vrije Universiteit Amsterdam
    Research Institute)

  • D. I. Boomsma

    (Vrije Universiteit Amsterdam
    Amsterdam Public Health Research Institute
    Research Institute)

  • A. Weihs

    (University Medicine Greifswald
    Site Rostock/Greifswald)

  • H. J. Grabe

    (University Medicine Greifswald
    Site Rostock/Greifswald)

  • L. Kühn

    (University Medicine Greifswald)

  • A. Teumer

    (University Medicine Greifswald
    Partner Site Greifswald)

  • H. Völzke

    (Partner Site Greifswald
    University Medicine Greifswald)

  • T. Zhu

    (University of Helsinki
    Minerva Foundation Institute for Medical Research)

  • J. Kaprio

    (University of Helsinki)

  • M. Ollikainen

    (University of Helsinki
    Minerva Foundation Institute for Medical Research)

  • F. S. David

    (School of Medicine & University Hospital Bonn
    University of Marburg)

  • S. Meinert

    (University of Münster
    University of Münster)

  • F. Stein

    (University of Marburg
    University of Marburg)

  • A. J. Forstner

    (School of Medicine & University Hospital Bonn
    Research Center Jülich
    University of Marburg)

  • U. Dannlowski

    (University of Münster)

  • T. Kircher

    (University of Marburg
    University of Marburg)

  • A. Tapuc

    (Max Planck School of Cognition
    Department Genes and Environment)

  • D. Czamara

    (Department Genes and Environment)

  • E. B. Binder

    (Department Genes and Environment)

  • T. Brückl

    (Department Genes and Environment)

  • A. S. F. Kwong

    (University of Edinburgh
    University of Bristol)

  • P. Yousefi

    (University of Bristol
    University of Bristol
    University Hospitals Bristol and Weston NHS Foundation Trust and University of Bristol)

  • C. C. Y. Wong

    (King’s College London)

  • L. Arseneault

    (King’s College London)

  • H. L. Fisher

    (King’s College London
    King’s College London)

  • J. Mill

    (University of Exeter)

  • S. R. Cox

    (University of Edinburgh)

  • P. Redmond

    (University of Edinburgh)

  • T. C. Russ

    (University of Edinburgh
    University of Edinburgh
    NHS Research Scotland)

  • E. J. C. G. Oord

    (Virginia Commonwealth University)

  • K. A. Aberg

    (Virginia Commonwealth University)

  • B. W. J. H. Penninx

    (Vrije Universiteit Amsterdam)

  • R. E. Marioni

    (University of Edinburgh)

  • N. R. Wray

    (University of Queensland
    University of Oxford)

  • A. M. McIntosh

    (University of Edinburgh)

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.

Suggested Citation

  • E. Davyson & X. Shen & F. Huider & M. J. Adams & K. Borges & D. L. McCartney & L. F. Barker & J. Dongen & D. I. Boomsma & A. Weihs & H. J. Grabe & L. Kühn & A. Teumer & H. Völzke & T. Zhu & J. Kaprio , 2025. "Insights from a methylome-wide association study of antidepressant exposure," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-024-55356-x
    DOI: 10.1038/s41467-024-55356-x
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    References listed on IDEAS

    as
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