Insights from a methylome-wide association study of antidepressant exposure

Eleanor Davyson(Edinburgh Cancer Research), Xueyi Shen(University of Edinburgh), Floris Huider(Vrije Universiteit Amsterdam), Mark J. Adams(University of Edinburgh), Karin Borges(University of Edinburgh), Daniel L. McCartney(Edinburgh Cancer Research), Lindsey Barker(The University of Queensland), Jenny van Dongen(Vrije Universiteit Amsterdam), Dorret I. Boomsma(Vrije Universiteit Amsterdam), Antoine Weihs(Universitätsmedizin Greifswald), Hans J. Grabe(Universitätsmedizin Greifswald), Annemarie Luise Kühn(Universitätsmedizin Greifswald), Alexander Teumer(Universitätsmedizin Greifswald), Henry Völzke(Universitätsmedizin Greifswald), Tianyu Zhu(University of Helsinki), Jaakko Kaprio(University of Helsinki), Miina Ollikainen(University of Helsinki), Friederike S. David(University of Bonn), Susanne Meinert(University of Münster), Frederike Stein(Philipps University of Marburg), Andreas J. Forstner(University of Bonn), Udo Dannlowski(University of Münster), Tilo Kircher(Philipps University of Marburg), A. Tapuc(Max Planck Institute for Human Cognitive and Brain Sciences), Darina Czamara(Max Planck Institute of Psychiatry), Elisabeth B. Binder(Max Planck Institute of Psychiatry), Tanja Brückl(Max Planck Institute of Psychiatry), Alex S. F. Kwong(University of Bristol), Paul Yousefi(University Hospitals Bristol NHS Foundation Trust), Chloe C. Y. Wong(King's College London), Louise Arseneault(King's College London), Helen L. Fisher(King's College London), Jonathan Mill(University of Exeter), Simon R. Cox(NHS Lothian), Paul Redmond(NHS Lothian), Tom C. Russ(Alzheimer Scotland), Edwin J. C. G. van den Oord(Virginia Commonwealth University), Karolina A. Åberg(Virginia Commonwealth University), Brenda W.J.H. Penninx(Amsterdam University Medical Centers), Riccardo E. Marioni(Edinburgh Cancer Research), Naomi R. Wray(The University of Queensland), Andrew M. McIntosh(University of Edinburgh)
Nature Communications
February 24, 2025
10.1038/s41467-024-55356-x
Cited by 7Open Access
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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.

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