Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Hauptstraße 5, 79104, Freiburg, Germany.
Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center-University of Freiburg, Hugstetter Straße 49, 79106, Freiburg, Germany.
Transl Psychiatry. 2022 Jun 1;12(1):221. doi: 10.1038/s41398-022-01996-w.
In adult patients with obsessive-compulsive disorder (OCD), altered DNA methylation has been discerned in several candidate genes, while DNA methylation on an epigenome-wide level has been investigated in only one Chinese study so far. Here, an epigenome-wide association study (EWAS) was performed in a sample of 76 OCD patients of European ancestry (37 women, age ± SD: 33.51 ± 10.92 years) and 76 sex- and age-matched healthy controls for the first time using the Illumina MethylationEPIC BeadChip. After quality control, nine epigenome-wide significant quantitative trait methylation sites (QTMs) and 21 suggestive hits were discerned in the final sample of 68 patients and 68 controls. The top hit (cg24159721) and four other significant QTMs (cg11894324, cg01070250, cg11330075, cg15174812) map to the region of the microRNA 12136 gene (MIR12136). Two additional significant CpG sites (cg05740793, cg20450977) are located in the flanking region of the MT-RNR2 (humanin) like 8 gene (MT-RNRL8), while two further QTMs (cg16267121, cg15890734) map to the regions of the MT-RNR2 (humanin) like 3 (MT-RNRL3) and MT-RNR2 (humanin) like 2 (MT-RNRL2) genes. Provided replication of the present findings in larger samples, the identified QTMs might provide more biological insight into the pathogenesis of OCD and thereby could in the future serve as peripheral epigenetic markers of OCD risk with the potential to inform targeted preventive and therapeutic efforts.
在患有强迫症（OCD）的成年患者中，已经在几个候选基因中发现了改变的 DNA 甲基化，而迄今为止，仅在中国的一项研究中研究了全基因组范围内的 DNA 甲基化。在这里，首次使用 Illumina MethylationEPIC BeadChip 在一个由 76 名欧洲血统的 OCD 患者（37 名女性，年龄 ± 标准差：33.51 ± 10.92 岁）和 76 名性别和年龄匹配的健康对照组成的样本中进行了全基因组关联研究（EWAS）。经过质量控制，在最终的 68 名患者和 68 名对照者样本中发现了 9 个全基因组显著的定量性状甲基化位点（QTM）和 21 个提示性命中。顶端命中（cg24159721）和其他 4 个显著的 QTM（cg11894324、cg01070250、cg11330075、cg15174812）映射到 microRNA 12136 基因（MIR12136）区域。另外两个显著的 CpG 位点（cg05740793、cg20450977）位于 MT-RNR2（humanin）样 8 基因（MT-RNRL8）的侧翼区域，而另外两个 QTM（cg16267121、cg15890734）映射到 MT-RNR2（humanin）样 3（MT-RNRL3）和 MT-RNR2（humanin）样 2（MT-RNRL2）基因的区域。如果在更大的样本中复制本研究的发现，所确定的 QTM 可能为 OCD 的发病机制提供更多的生物学见解，从而有可能在未来作为 OCD 风险的外周表观遗传标志物，并有可能为有针对性的预防和治疗努力提供信息。
