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. SteinA. 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*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

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.
Original languageEnglish
Article number1908
Number of pages15
JournalNature Communications
Volume16
Issue number1
Early online date24 Feb 2025
DOIs
Publication statusE-pub ahead of print - 24 Feb 2025

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© The Author(s) 2025.

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