Insights from a methylome-wide association study of antidepressant exposure

IF 15.7 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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抗抑郁药物暴露甲基组关联研究的见解

本研究采用自我报告和处方衍生测量方法，对苏格兰一代（GS）16531 人的全血 DNA 甲基化与抗抑郁药暴露的关联性进行了测试。我们发现了 8 项关联，自我报告和处方衍生测量结果高度一致。性别分层分析发现，女性对四个 CpGs 的效应估计值有明显增加。在杏仁核中表达并注释为突触小泡膜本体的基因出现了富集。两个 CpGs（cg15071067；DGUOK-AS1 和 cg26277237；KANK1）显示出 DNA 甲基化与治疗时间的相关性。前 1%的 CpGs 与另一项独立的抗抑郁药暴露全甲基化关联研究有明显重叠。最后，在对八个独立的外部数据集进行的荟萃分析中，对该样本进行的甲基化特征评分显示与抗抑郁药物暴露有显著关联。在这项关于抗抑郁药物暴露与 DNA 甲基化的大型调查中，我们证明了两者之间存在着密切的联系，这值得我们进一步研究，以便为设计更有效、更耐受的抑郁症治疗方法提供信息。

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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.