Insights from a methylome-wide association study of antidepressant exposure

IF 14.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Nature Communications Pub Date : 2025-02-24 DOI:10.1038/s41467-024-55356-x

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

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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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来源期刊

Nature Communications Biological Science Disciplines-

CiteScore

24.90

自引率

2.40%

发文量

6928

审稿时长

3.7 months

期刊介绍： Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.