Abstract：
Tardive dyskinesia (TD) develops in 20-30% of schizophrenia patients and up to 50% in patients > 50 years old. DNA methylation may play an important role in the development of TD.
DNA methylation analyses in schizophrenia with TD.
We conducted a genome-wide DNA methylation analysis in schizophrenia with TD using methylated DNA immunoprecipitation coupled with next-generation sequencing (MeDIP-Seq) in a Chinese sample including five schizophrenia patients with TD and five without TD (NTD), and five healthy controls. The results were expressed as the log2FC, fold change of normalized tags between two groups within the differentially methylated region (DMR). For validation, the pyrosequencing was used to quantify DNA methylation levels of several methylated genes in an independent sample (n = 30).
Through genome-wide MeDIP-Seq analysis, we identified 116 genes that were significantly differentially methylated in promotor regions in comparison of TD group with NTD group including 66 hypermethylated genes (top 4 genes are GABRR1, VANGL2, ZNF534, and ZNF746) and 50 hypomethylated genes (top 4 genes are DERL3, GSTA4, KNCN, and LRRK1). Part of these genes (such as DERL3, DLGAP2, GABRR1, KLRG2, LRRK1, VANGL2, and ZP3) were previously reported to be associated with methylation in schizophrenia. Gene Ontology enrichment and KEGG pathway analyses identified several pathways. So far, we have confirmed the methylation of 3 genes (ARMC6, WDR75, and ZP3) in schizophrenia with TD using pyrosequencing.
This study identified number of methylated genes and pathways for TD and will provide potential biomarkers for TD and serve as a resource for replication in other populations.
DNA methylation analyses in schizophrenia with TD.
We conducted a genome-wide DNA methylation analysis in schizophrenia with TD using methylated DNA immunoprecipitation coupled with next-generation sequencing (MeDIP-Seq) in a Chinese sample including five schizophrenia patients with TD and five without TD (NTD), and five healthy controls. The results were expressed as the log2FC, fold change of normalized tags between two groups within the differentially methylated region (DMR). For validation, the pyrosequencing was used to quantify DNA methylation levels of several methylated genes in an independent sample (n = 30).
Through genome-wide MeDIP-Seq analysis, we identified 116 genes that were significantly differentially methylated in promotor regions in comparison of TD group with NTD group including 66 hypermethylated genes (top 4 genes are GABRR1, VANGL2, ZNF534, and ZNF746) and 50 hypomethylated genes (top 4 genes are DERL3, GSTA4, KNCN, and LRRK1). Part of these genes (such as DERL3, DLGAP2, GABRR1, KLRG2, LRRK1, VANGL2, and ZP3) were previously reported to be associated with methylation in schizophrenia. Gene Ontology enrichment and KEGG pathway analyses identified several pathways. So far, we have confirmed the methylation of 3 genes (ARMC6, WDR75, and ZP3) in schizophrenia with TD using pyrosequencing.
This study identified number of methylated genes and pathways for TD and will provide potential biomarkers for TD and serve as a resource for replication in other populations.
摘要：
背景：迟发性运动障碍（TD）在20-30％的精神分裂症患者中发生，在50岁以上的患者中高达50％。DNA甲基化可能在TD的发生发展中起重要作用。
目的：精神分裂症伴TD的DNA甲基化分析。
方法：我们使用甲基化DNA免疫沉淀结合下一代测序（MeDIP-Seq）对患有TD的精神分裂症患者进行了全基因组DNA甲基化分析，其中包括5名患有TD的精神分裂症患者和5名没有TD（NTD）。和五个健康对照。结果表示为log2FC，差异甲基化区域（DMR）内两组之间标准化标签的倍数变化。对于验证，焦磷酸测序用于量化独立样本中几个甲基化基因的DNA甲基化水平(n=30).
结果：通过全基因组MeDIP-Seq分析，我们鉴定出116个基因在启动子区显着差异甲基化TD组与NTD组相比，包括66个高甲基化基因（前4个基因是GABRR1，VANGL2，ZNF534和ZNF746）和50个低甲基化基因（前4个基因是DERL3，GSTA4，KNCN，和LRRK1）。这些基因的一部分（例如DERL3，DLGAP2，GABRR1，KLRG2，LRRK1，VANGL2和ZP3）先前被报道与精神分裂症中的甲基化有关。基因本体论富集和KEGG途径分析确定了几种途径。到目前为止,我们使用焦磷酸测序证实了精神分裂症伴TD的3个基因(ARMC6,WDR75和ZP3)的甲基化.
结论：这项研究确定了TD的甲基化基因和通路的数量，并将为TD提供潜在的生物标志物，并作为在其他群体中复制的资源。
目的：精神分裂症伴TD的DNA甲基化分析。
方法：我们使用甲基化DNA免疫沉淀结合下一代测序（MeDIP-Seq）对患有TD的精神分裂症患者进行了全基因组DNA甲基化分析，其中包括5名患有TD的精神分裂症患者和5名没有TD（NTD）。和五个健康对照。结果表示为log2FC，差异甲基化区域（DMR）内两组之间标准化标签的倍数变化。对于验证，焦磷酸测序用于量化独立样本中几个甲基化基因的DNA甲基化水平(n=30).
结果：通过全基因组MeDIP-Seq分析，我们鉴定出116个基因在启动子区显着差异甲基化TD组与NTD组相比，包括66个高甲基化基因（前4个基因是GABRR1，VANGL2，ZNF534和ZNF746）和50个低甲基化基因（前4个基因是DERL3，GSTA4，KNCN，和LRRK1）。这些基因的一部分（例如DERL3，DLGAP2，GABRR1，KLRG2，LRRK1，VANGL2和ZP3）先前被报道与精神分裂症中的甲基化有关。基因本体论富集和KEGG途径分析确定了几种途径。到目前为止,我们使用焦磷酸测序证实了精神分裂症伴TD的3个基因(ARMC6,WDR75和ZP3)的甲基化.
结论：这项研究确定了TD的甲基化基因和通路的数量，并将为TD提供潜在的生物标志物，并作为在其他群体中复制的资源。
