DNA methylation may partly explain psychotropic drug-induced metabolic side effects: results from a prospective 1-month observational study.
Détails
Télécharger: 38419113.pdf (1379.44 [Ko])
Etat: Public
Version: Final published version
Licence: CC BY 4.0
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
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
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.
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