DNA methylation may partly explain psychotropic drug-induced metabolic side effects: results from a prospective 1-month observational study.

Détails

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Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_37368679B832
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
DNA methylation may partly explain psychotropic drug-induced metabolic side effects: results from a prospective 1-month observational study.
Périodique
Clinical epigenetics
Auteur⸱e⸱s
Dubath C., Porcu E., Delacrétaz A., Grosu C., Laaboub N., Piras M., von Gunten A., Conus P., Plessen K.J., Kutalik Z., Eap C.B.
ISSN
1868-7083 (Electronic)
ISSN-L
1868-7075
Statut éditorial
Publié
Date de publication
28/02/2024
Peer-reviewed
Oui
Volume
16
Numéro
1
Pages
36
Langue
anglais
Notes
Publication types: Observational Study ; Journal Article
Publication Status: epublish
Résumé
Metabolic side effects of psychotropic medications are a major drawback to patients' successful treatment. Using an epigenome-wide approach, we aimed to investigate DNA methylation changes occurring secondary to psychotropic treatment and evaluate associations between 1-month metabolic changes and both baseline and 1-month changes in DNA methylation levels. Seventy-nine patients starting a weight gain inducing psychotropic treatment were selected from the PsyMetab study cohort. Epigenome-wide DNA methylation was measured at baseline and after 1 month of treatment, using the Illumina Methylation EPIC BeadChip.
A global methylation increase was noted after the first month of treatment, which was more pronounced (p < 2.2 × 10 <sup>-16</sup> ) in patients whose weight remained stable (< 2.5% weight increase). Epigenome-wide significant methylation changes (p < 9 × 10 <sup>-8</sup> ) were observed at 52 loci in the whole cohort. When restricting the analysis to patients who underwent important early weight gain (≥ 5% weight increase), one locus (cg12209987) showed a significant increase in methylation levels (p = 3.8 × 10 <sup>-8</sup> ), which was also associated with increased weight gain in the whole cohort (p = 0.004). Epigenome-wide association analyses failed to identify a significant link between metabolic changes and methylation data. Nevertheless, among the strongest associations, a potential causal effect of the baseline methylation level of cg11622362 on glycemia was revealed by a two-sample Mendelian randomization analysis (n = 3841 for instrument-exposure association; n = 314,916 for instrument-outcome association).
These findings provide new insights into the mechanisms of psychotropic drug-induced weight gain, revealing important epigenetic alterations upon treatment, some of which may play a mediatory role.
Mots-clé
Humans, DNA Methylation, Epigenesis, Genetic, Prospective Studies, Genome-Wide Association Study/methods, Weight Gain/genetics, Psychotropic Drugs/adverse effects, DNA methylation, EWAS, Metabolic side effects, Psychotropic drugs
Pubmed
Web of science
Open Access
Oui
Création de la notice
01/03/2024 9:32
Dernière modification de la notice
05/12/2024 14:34
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