Antidepressant Exposure and DNA Methylation: Insights from a Methylome-Wide Association Study.
Autor: | Davyson E, Shen X, Huider F, Adams M, Borges K, McCartney D, Barker L, Van Dongen J, Boomsma D, Weihs A, Grabe H, Kühn L, Teumer A, Völzke H, Zhu T, Kaprio J, Ollikainen M, David FS, Meinert S, Stein F, Forstner AJ, Dannlowski U, Kircher T, Tapuc A, Czamara D, Binder EB, Brückl T, Kwong A, Yousefi P, Wong C, Arseneault L, Fisher HL, Mill J, Cox S, Redmond P, Russ TC, van den Oord E, Aberg KA, Penninx B, Marioni RE, Wray NR, McIntosh AM |
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Jazyk: | angličtina |
Zdroj: | MedRxiv : the preprint server for health sciences [medRxiv] 2024 May 03. Date of Electronic Publication: 2024 May 03. |
DOI: | 10.1101/2024.05.01.24306640 |
Abstrakt: | Importance: Understanding antidepressant mechanisms could help design more effective and tolerated treatments. Objective: Identify DNA methylation (DNAm) changes associated with antidepressant exposure. Design: Case-control methylome-wide association studies (MWAS) of antidepressant exposure were performed from blood samples collected between 2006-2011 in Generation Scotland (GS). The summary statistics were tested for enrichment in specific tissues, gene ontologies and an independent MWAS in the Netherlands Study of Depression and Anxiety (NESDA). A methylation profile score (MPS) was derived and tested for its association with antidepressant exposure in eight independent cohorts, alongside prospective data from GS. Setting: Cohorts; GS, NESDA, FTC, SHIP-Trend, FOR2107, LBC1936, MARS-UniDep, ALSPAC, E-Risk, and NTR. Participants: Participants with DNAm data and self-report/prescription derived antidepressant exposure. Main Outcomes and Measures: Whole-blood DNAm levels were assayed by the EPIC/450K Illumina array (9 studies, N Results: The self-report MWAS (N = 16,536, N Conclusions and Relevance: Antidepressant exposure is associated with changes in DNAm across different cohorts. Further investigation into these changes could inform on new targets for antidepressant treatments. 3 Key Points: Question: Is antidepressant exposure associated with differential whole blood DNA methylation? Findings: In this methylome-wide association study of 16,536 adults across Scotland, antidepressant exposure was significantly associated with hypermethylation at CpGs mapping to KANK1 and DGUOK-AS1. A methylation profile score trained on this sample was significantly associated with antidepressant exposure (pooled f3 [95%CI]=0.196 [0.105, 0.288], p < 1x10 -4 ) in a meta-analysis of external datasets. Meaning: Antidepressant exposure is associated with hypermethylation at KANK1 and DGUOK-AS1 , which have roles in mitochondrial metabolism and neurite outgrowth. If replicated in future studies, targeting these genes could inform the design of more effective and better tolerated treatments for depression. |
Databáze: | MEDLINE |
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