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The DNA methylome in panic disorder: a case-control and longitudinal psychotherapy-epigenetic study.
Translational Psychiatry ( IF 5.8 ) Pub Date : 2019-11-21 , DOI: 10.1038/s41398-019-0648-6
Christiane Ziegler 1 , Franziska Grundner-Culemann 2 , Miriam A Schiele 1 , Pascal Schlosser 2 , Leonie Kollert 3 , Marina Mahr 3 , Agnieszka Gajewska 3 , Klaus-Peter Lesch 4, 5, 6 , Jürgen Deckert 3 , Anna Köttgen 2 , Katharina Domschke 1, 7
Affiliation  

In panic disorder (PD), epigenetic mechanisms such as DNA methylation of candidate genes have been suggested to play a key role at the intersection of genetic and environmental factors. On an epigenome-wide level, however, only two studies in PD patients have been published so far, while to date no study has intra-individually analyzed dynamic epigenetic correlates of treatment-response in PD on a DNA methylome level. Here, an epigenome-wide association study (EWAS) was performed in a sample of 57 PD patients and matched healthy controls using the Illumina MethylationEPIC BeadChip, along with a longitudinal approach assessing changes on the DNA methylome level corresponding to clinical effects of a manualized six-week cognitive-behavioral therapy (CBT) in PD. While no epigenome-wide significant hits could be discerned, top suggestive evidence was observed for decreased methylation in PD at cg19917903 in the Cilia and Flagella Associated Protein 46 (CFAP46) gene, and for an increase in methylation after CBT at cg06943668 in the Interleukin 1 Receptor Type 1 (IL1R1) gene in treatment responders to CBT. Additional exploratory analyses based on biological validity and a combined statistical/biological ranking point to further new potential PD risk genes such as the CCL4L1 or GMNN genes, and suggest dynamic methylation of, e.g., the ZFP622 and the SLC43A2 genes along with response to CBT. These EWAS and first longitudinal epigenome-wide pilot data in PD add to the emerging candidate gene-based body of evidence for epigenetic mechanisms to be involved in PD pathogenesis and to possibly constitute dynamic biological correlates of therapeutic interventions.

中文翻译:

惊恐症中的DNA甲基化组:病例对照和纵向心理治疗表观遗传研究。

在恐慌症(PD)中,已提出表观遗传机制(例如候选基因的DNA甲基化)在遗传和环境因素的交汇处起关键作用。然而,到目前为止,在表观基因组范围内,仅发表了两项针对PD患者的研究,而迄今为止,尚无研究在DNA甲基基因组水平上对PD中PD治疗反应的动态表观遗传学相关性进行个体内分析。在这里,使用Illumina甲基化EPIC BeadChip在57名PD患者和匹配的健康对照样本中进行了表观基因组关联研究(EWAS),同时采用纵向方法评估了DNA甲基化水平的变化,这对应于手动操作的六个PD的每周认知行为疗法(CBT)。尽管无法识别出整个表观基因组范围内的重大事件,提示:在治疗应答者中,纤毛和鞭毛相关蛋白46(CFAP46)基因中cg19917903的PD甲基化降低,cg06943668的CBT后,cG06943668的1型白细胞介素1受体基因(IL1R1)甲基化增加。 CBT。基于生物学有效性和综合的统计/生物学排名的其他探索性分析指向其他新的潜在PD风险基因,例如CCL4L1或GMNN基因,并建议ZFP622和SLC43A2基因动态甲基化以及对CBT的反应。这些EWAS和PD中的第一个纵向表观基因组范围的先导数据为基于PD发病机制的表观遗传机制增加了新的基于候选基因的证据,并可能构成了治疗干预措施的动态生物学关联。
更新日期:2019-11-22
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