DNA methylation in the superior temporal gyrus of 44 subjects with schizophrenia and 44 non-psychiatric control subjects

DNA methylation (DNAm) signal from the planum temporale of superior temporal gyrus (STG) of forty-four subjects with schizophrenia (SZ) and forty-four non-psychiatric control (NPC) subjects was measured on the Illumina MethylationEPIC BeadChip Infinium (EPIC) array. Averaged, normalized beta-values at each site were correlated with dendritic spine density (DSD) previously measured per subject to identify site-specific DNAm-DSD correlations that met methylome-wide significance, or a suggestive-level of significance. We tested the hypothesis that DNAm correlates with DSD in human STG at several sites across the methylome and that this relationship is disrupted in SZ. DSD measures were available for 40 of the subjects with SZ and 40 of the NPC subjects. We found DNAm to correlate with DSD at more sites than expected by chance in NPC, but not SZ, subjects. In addition, we show that the slopes of the linear DNAm-DSD correlations differed between SZ and NPC subjects at more sites than expected by chance. Together, these data suggest that alterations in the intercation between DNAm and neurobiology in SZ may be a mechanism for SZ-related DSD reductions. A total of 96 genomic DNA samples taken from postmortem STG of subjects with SZ (N=44, with 4 subjects replicated) and NPC subjects (N=44, with 4 subjects replicated) were bisulfite converted and hybridized to the probes on the EPIC array. SZ: Schizophrenia NPC: Non-psychiatric control STG: Superior temporal gyrus (of human brain)

本研究针对44名精神分裂症（schizophrenia, SZ）患者与44名非精神疾病对照（non-psychiatric control, NPC）受试者的颞上回（superior temporal gyrus, STG）颞平面组织的DNA甲基化（DNA methylation, DNAm）信号，采用Illumina MethylationEPIC BeadChip Infinium（EPIC）芯片进行检测。将每个位点经标准化处理后的平均β值，与此前针对每名受试者测得的树突棘密度（dendritic spine density, DSD）进行相关性分析，以筛选符合全甲基化组显著性水平或提示性显著性水平的位点特异性DNAm-DSD关联。本研究验证了两项假设：其一，人类STG的全甲基化组中存在多个位点的DNAm与DSD存在关联；其二，该关联在SZ患者中存在紊乱。其中40名SZ患者与40名NPC受试者拥有完整的DSD检测数据。研究结果显示，在NPC受试者中，DNAm与DSD存在关联的位点数量显著高于随机预期水平，而SZ患者中未观察到该现象。此外，本研究还发现，SZ患者与NPC受试者之间的线性DNAm-DSD关联斜率存在显著差异的位点数量，同样高于随机预期水平。综上，上述结果提示，SZ患者体内DNAm与神经生物学过程之间的交互作用异常，可能是导致SZ相关DSD降低的潜在机制。本研究共纳入96份来自死后大脑STG组织的基因组DNA样本，其中SZ患者样本44份（含4份重复样本），NPC受试者样本44份（含4份重复样本）；所有样本均经亚硫酸氢盐转化后，与EPIC芯片上的探针进行杂交。术语说明：SZ代表精神分裂症，NPC代表非精神疾病对照，STG代表人类大脑颞上回。