Céline Dubath, Eleonora Porcu, Aurélie Delacrétaz, Claire Grosu, Nermine Laaboub, Marianna Piras, Armin von Gunten, Philippe Conus, Kerstin Jessica Plessen, Zoltán Kutalik, Chin Bin Eap
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Epigenome-wide DNA methylation was measured at baseline and after 1 month of treatment, using the Illumina Methylation EPIC BeadChip.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"16 1","pages":"36"},"PeriodicalIF":4.8000,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10903022/pdf/","citationCount":"0","resultStr":"{\"title\":\"DNA methylation may partly explain psychotropic drug-induced metabolic side effects: results from a prospective 1-month observational study.\",\"authors\":\"Céline Dubath, Eleonora Porcu, Aurélie Delacrétaz, Claire Grosu, Nermine Laaboub, Marianna Piras, Armin von Gunten, Philippe Conus, Kerstin Jessica Plessen, Zoltán Kutalik, Chin Bin Eap\",\"doi\":\"10.1186/s13148-024-01648-4\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Metabolic side effects of psychotropic medications are a major drawback to patients' successful treatment. 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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. 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引用次数: 0
摘要
背景:精神药物的代谢副作用是影响患者成功治疗的一个主要因素。我们采用了一种全表观基因组方法,旨在研究精神药物治疗后继发的DNA甲基化变化,并评估1个月代谢变化与DNA甲基化水平基线和1个月变化之间的关联。从PsyMetab研究队列中挑选了79名开始接受体重增加诱导性精神药物治疗的患者。使用 Illumina Methylation EPIC BeadChip 对基线和治疗 1 个月后的全表观基因组 DNA 甲基化进行了测量:结果:在整个队列的 52 个位点上观察到,治疗第一个月后,全基因组甲基化增加,体重保持稳定的患者甲基化增加更明显(p -16)(-8)。当把分析范围限制在早期体重明显增加(体重增加≥5%)的患者时,有一个位点(cg12209987)的甲基化水平显著增加(p = 3.8 × 10-8),这也与整个队列中体重增加有关(p = 0.004)。全表观基因组关联分析未能发现代谢变化与甲基化数据之间的重要联系。然而,在最强的关联中,通过双样本孟德尔随机分析(工具-暴露关联 n = 3841;工具-结果关联 n = 314 916)发现了 cg11622362 基线甲基化水平对血糖的潜在因果效应:这些研究结果为了解精神药物诱发体重增加的机制提供了新的视角,揭示了治疗过程中重要的表观遗传学改变,其中一些可能起到了中介作用。
DNA methylation may partly explain psychotropic drug-induced metabolic side effects: results from a prospective 1-month observational study.
Background: 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.
Results: A global methylation increase was noted after the first month of treatment, which was more pronounced (p < 2.2 × 10-16) in patients whose weight remained stable (< 2.5% weight increase). Epigenome-wide significant methylation changes (p < 9 × 10-8) 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 × 10-8), 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).
Conclusion: 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.
期刊介绍:
Clinical Epigenetics, the official journal of the Clinical Epigenetics Society, is an open access, peer-reviewed journal that encompasses all aspects of epigenetic principles and mechanisms in relation to human disease, diagnosis and therapy. Clinical trials and research in disease model organisms are particularly welcome.