Abstract：
BACKGROUND: Epigenetic modifications, such as DNA methylation, contribute to the pathophysiology of major depressive disorder (MDD). This study aimed to identify novel MDD-associated epigenetic loci using DNA methylation profiles and explore the correlations between epigenetic loci and cortical thickness changes in patients with MDD.
METHODS: A total of 350 patients with MDD and 161 healthy controls (HCs) were included in the epigenome-wide association studies (EWAS). We analyzed methylation, copy number alteration (CNA), and gene network profiles in the MDD group. A total of 234 patients with MDD and 135 HCs were included in neuroimaging methylation analysis. Pearson\'s partial correlation analysis was used to estimate the correlation between cortical thickness of brain regions and DNA methylation levels of the loci.
RESULTS: In total, 2018 differentially methylated probes (DMPs) and 351 differentially methylated regions (DMRs) were identified. DMP-related genes were enriched in two networks involved in the central nervous system. In neuroimaging analysis, patients with MDD showed cortical thinning in the prefrontal regions and cortical thickening in several occipital regions. Cortical thickness of the left ventrolateral prefrontal cortex (VLPFC, i.e. pars triangularis) was negatively correlated with eight DMPs associated with six genes (EML6, ZFP64, CLSTN3, KCNMA1, TAOK2, and NT5E).
CONCLUSIONS: Through combining DNA methylation and neuroimaging analyses, negative correlations were identified between the cortical thickness of the left VLPFC and DNA methylation levels of eight DMPs. Our findings could improve our understanding of the pathophysiology of MDD.
METHODS: A total of 350 patients with MDD and 161 healthy controls (HCs) were included in the epigenome-wide association studies (EWAS). We analyzed methylation, copy number alteration (CNA), and gene network profiles in the MDD group. A total of 234 patients with MDD and 135 HCs were included in neuroimaging methylation analysis. Pearson\'s partial correlation analysis was used to estimate the correlation between cortical thickness of brain regions and DNA methylation levels of the loci.
RESULTS: In total, 2018 differentially methylated probes (DMPs) and 351 differentially methylated regions (DMRs) were identified. DMP-related genes were enriched in two networks involved in the central nervous system. In neuroimaging analysis, patients with MDD showed cortical thinning in the prefrontal regions and cortical thickening in several occipital regions. Cortical thickness of the left ventrolateral prefrontal cortex (VLPFC, i.e. pars triangularis) was negatively correlated with eight DMPs associated with six genes (EML6, ZFP64, CLSTN3, KCNMA1, TAOK2, and NT5E).
CONCLUSIONS: Through combining DNA methylation and neuroimaging analyses, negative correlations were identified between the cortical thickness of the left VLPFC and DNA methylation levels of eight DMPs. Our findings could improve our understanding of the pathophysiology of MDD.
摘要：
背景：表观遗传修饰，比如DNA甲基化，有助于重度抑郁症（MDD）的病理生理学。这项研究旨在使用DNA甲基化图谱鉴定新的MDD相关表观遗传位点，并探索MDD患者表观遗传位点与皮质厚度变化之间的相关性。
方法：共有350例MDD患者和161例健康对照（HCs）纳入了表观全基因组关联研究（EWAS）。我们分析了甲基化,拷贝数变更(CNA),和MDD组中的基因网络概况。共234例MDD患者和135例HCs患者纳入神经影像学甲基化分析。使用Pearson的偏相关分析来估计脑区皮质厚度与基因座DNA甲基化水平之间的相关性。
结果：总计，鉴定了2018年差异甲基化探针（DMPs）和351个差异甲基化区域（DMRs）。DMP相关基因富集在涉及中枢神经系统的两个网络中。在神经影像分析中，MDD患者的前额叶区域皮质变薄,多个枕骨区域皮质增厚.左腹外侧前额叶皮质的皮质厚度（VLPFC，即三角条）与与六个基因（EML6，ZFP64，CLSTN3，KCNMA1，TAOK2和NT5E）相关的八个DMPs呈负相关。
结论：通过结合DNA甲基化和神经影像学分析，左VLPFC的皮质厚度与8个DMPs的DNA甲基化水平呈负相关.我们的发现可以提高我们对MDD病理生理学的理解。
方法：共有350例MDD患者和161例健康对照（HCs）纳入了表观全基因组关联研究（EWAS）。我们分析了甲基化,拷贝数变更(CNA),和MDD组中的基因网络概况。共234例MDD患者和135例HCs患者纳入神经影像学甲基化分析。使用Pearson的偏相关分析来估计脑区皮质厚度与基因座DNA甲基化水平之间的相关性。
结果：总计，鉴定了2018年差异甲基化探针（DMPs）和351个差异甲基化区域（DMRs）。DMP相关基因富集在涉及中枢神经系统的两个网络中。在神经影像分析中，MDD患者的前额叶区域皮质变薄,多个枕骨区域皮质增厚.左腹外侧前额叶皮质的皮质厚度（VLPFC，即三角条）与与六个基因（EML6，ZFP64，CLSTN3，KCNMA1，TAOK2和NT5E）相关的八个DMPs呈负相关。
结论：通过结合DNA甲基化和神经影像学分析，左VLPFC的皮质厚度与8个DMPs的DNA甲基化水平呈负相关.我们的发现可以提高我们对MDD病理生理学的理解。
