Correlation between DNA methylation and gene expression in the brains of patients with bipolar disorder and schizophrenia.

Correlation between DNA methylation and gene expression in the brains of patients with bipolar disorder and schizophrenia.
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DOI:
10.1111/bdi.12255
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发表时间:
2014-12
期刊:
影响因子:
5.4
通讯作者:
Liu C
Liu C
中科院分区:
医学2区
文献类型:
--
作者:
Chen C;Zhang C;Cheng L;Reilly JL;Bishop JR;Sweeney JA;Chen HY;Gershon ES;Liu C

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异常的DNA甲基化和基因表达在精神病患者死后脑组织中有报道,但到目前为止,还没有系统的评估甲基化和表达在脑组织全基因组范围内的协同变化。本研究对39例精神分裂症患者、36例双相情感障碍患者和43例未受影响的对照组的小脑样本进行了全基因组甲基化和表达分析,以筛选基因表达与CpG甲基化的相关性。在整个基因组中检测的71,753对CpG基因对(CpG Gene Pairs, cgp)中,经多次检测校正后发现204对与基因表达显著相关[p < 0.05,错误发现率(false discovery rate, FDR) q < 0.05]。通过比较患有双相情感障碍和精神分裂症的精神病患者与健康对照,检测相关的cgp的疾病相关表达和甲基化。发现其中4种cgp与精神病患者PIK3R1、BTN3A3、NHLH1和SLC16A7的差异表达和甲基化显著相关(p < 0.05, FDR q < 0.2)。额外的表达和甲基化数据集被用来验证DNA甲基化、基因表达和神经精神疾病之间的关系。这些结果表明,鉴定出的具有异常甲基化模式的差异表达基因可以代表神经精神疾病病因和病理的新候选因素。
Aberrant DNA methylation and gene expression have been reported in postmortem brain tissues of psychotic patients, but until now there has been no systematic evaluation of synergistic changes in methylation and expression on a genome-wide scale from brain tissue. In this study, genome-wide methylation and expression analysis were performed on cerebellum samples from 39 patients with schizophrenia, 36 patients with bipolar disorder, and 43 unaffected controls, to screen for the correlation in gene expression and CpG methylation. Out of 71,753 CpG Gene Pairs (CGPs) tested across the genome, 204 were found to significantly correlate with gene expression after correction for multiple testing [p < 0.05, false discovery rate (FDR) q < 0.05]. The correlated CGPs were tested for disease-associated expression and methylation by comparing psychotic patients with bipolar disorder and schizophrenia to healthy controls. Four of the identified CGPs were found to significantly correlate with the differential expression and methylation of the PIK3R1, BTN3A3, NHLH1, and SLC16A7 in psychotic patients (p < 0.05, FDR q < 0.2). Additional expression and methylation datasets were used to validate the relationship between DNA methylation, gene expression, and neuropsychiatric diseases. These results suggest that the identified differentially expressed genes with an aberrant methylation pattern can represent novel candidate factors in the etiology and pathology of neuropsychiatric disorders.
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发表时间: 2013-12
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