In this study, we investigate the epigenetic mechanisms associated with current suicidal ideation. Gene expression changes have been found in post-mortem brain of suicide victims. However, it is not clear how in-vivo gene expression change confers risk for suicide. DNA methylation is a form of epigenetic modification that regulates gene expression. Our primary aim is to investigate genome-wide methylation in conferring risk for current suicidal ideation (SI) in schizophrenia. The presence of current SI and genome-wide methylation patterns were assessed in 107 patients with schizophrenia. DNA methylation has been measured in white blood cells as a possible peripheral biomarker of SI. SI was the primary outcome variable in a model including methylation status of white blood cells using the Illumina 450 array. We have tested the association with genome-wide methylation levels in 19 subjects with current SI and 88 subjects without current SI and we found that higher methylation level in the CpG cg06121808 located in the gene SLC20A1 on chromosome 2 was associated with current SI (p = 0.000003; beta difference = 0.06). Furthermore, the distal promoter analysis showed that the gene SMPD2 was hypermethylated in suicide ideators (p = 0.0001; beta difference = 0.02). Thus, molecular biomarkers could advance our understanding of the molecular mechanisms of stress-related SI. Furthermore, the methylation sites that we have identified should be replicated in other suicide related phenotypes to generate robust biomarkers with high translational value for proof of concept interventions aiming at reducing SI.

在这项研究中，我们调查了与当前自杀意念相关的表观遗传机制。在自杀受害者的死后大脑中发现了基因表达变化。然而，尚不清楚体内基因表达变化如何导致自杀风险。DNA甲基化是一种调节基因表达的表观遗传修饰形式。我们的主要目的是研究全基因组甲基化对精神分裂症当前自杀意念 (SI) 风险的影响。在 107 名精神分裂症患者中评估了当前 SI 和全基因组甲基化模式的存在。已在白细胞中测量 DNA 甲基化作为 SI 的可能外周生物标志物。SI 是模型中的主要结果变量，包括使用 Illumina 450 阵列的白细胞甲基化状态。p  = 0.000003；贝塔差 = 0.06）。此外，远端启动子分析显示 SMPD2 基因在自杀意念者中高度甲基化（p  = 0.0001；β 差异 = 0.02）。因此，分子生物标志物可以促进我们对压力相关 SI 的分子机制的理解。此外，我们已经确定的甲基化位点应该在其他与自杀相关的表型中复制，以产生具有高转化价值的强大生物标志物，用于旨在降低 SI 的概念干预证明。