DNA methylation and inflammation marker profiles associated with a history of depression
DNA methylation and inflammation marker profiles associated with a history of depression
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DOI：
10.1093/hmg/ddy199
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发表时间：
2018-08-15
影响因子：
3.5
通讯作者：
Murphy, Therese M.
中科院分区：
文献类型：
--
作者：
Crawford, Bethany;Craig, Zoe;Murphy, Therese M.
抑郁症是一种常见的致残性疾病，是一个重大的社会和经济健康问题。此外，抑郁症与具有炎性病因的疾病的进展相关，包括许多炎性相关病症。在分子水平上，抑郁症可能促进这些疾病的发病和相关免疫功能障碍的机制还不清楚。在这项研究中，我们使用Illumine 450 K微阵列评估了来自自我报告有抑郁症史的个体（n = 100）和没有抑郁症史的个体（n = 100）的全血DNA中DNA甲基化的全基因组模式。我们的分析确定了6个显著的（Sidak校正P < 0.05）抑郁相关差异甲基化区域（DMR）;排名第一的DMR位于LTB 4 R2基因的外显子1（Sidel校正P = 1.27 x 10（-14））。生成抑郁症的多基因风险评分（PRS），并分别在DNA和血清样本中测量已知的炎症生物标志物端粒长度（TL）和IL-6。接下来，我们采用了系统水平的方法，以确定网络的共甲基化基因座与抑郁症的历史，除了抑郁症PRS，TL和IL-6水平。我们的分析确定了一个抑郁症相关的共甲基化模块（P = 0.04）。有趣的是，抑郁相关模块高度富集与免疫功能相关的途径，并且还与TL和IL-6细胞因子水平相关。总之，我们的全基因组DNA甲基化分析有和没有自我报告的抑郁症病史的个人确定了几个候选的DMR的抑郁症的发病机制及其相关的免疫功能障碍表型的潜在相关性。
Depression is a common and disabling disorder, representing a major social and economic health issue. Moreover, depression is associated with the progression of diseases with an inflammatory etiology including many inflammatory related disorders. At the molecular level, the mechanisms by which depression might promote the onset of these diseases and associated immune-dysfunction are not well understood. In this study we assessed genome-wide patterns of DNA methylation in whole blood-derived DNA obtained from individuals with a self-reported history of depression (n = 100) and individuals without a history of depression (n = 100) using the Illumine 450K microarray. Our analysis identified six significant (Sidak corrected P < 0.05) depression-associated differentially methylated regions (DMRs); the top-ranked DMR was located in exon 1 of the LTB4R2 gene (Sidel corrected P = 1.27 x 10(-14)). Polygenic risk scores (PRS) for depression were generated and known biological markers of inflammation, telomere length (TL) and IL-6, were measured in DNA and serum samples, respectively. Next, we employed a systems-level approach to identify networks of co-methylated loci associated with a history of depression, in addition to depression PRS, TL and IL-6 levels. Our analysis identified one depression-associated co-methylation module (P = 0.04). Interestingly, the depression-associated module was highly enriched for pathways related to immune function and was also associated with TL and IL-6 cytokine levels. In summary, our genome-wide DNA methylation analysis of individuals with and without a self-reported history of depression identified several candidate DMRs of potential relevance to the pathogenesis of depression and its associated immune-dysfunction phenotype.