Trans-omics pathway analysis suggests that eQTLs contribute to chondrocyte apoptosis of Kashin-Beck disease through regulating apoptosis pathway expression.
Trans-omics pathway analysis suggests that eQTLs contribute to chondrocyte apoptosis of Kashin-Beck disease through regulating apoptosis pathway expression.
复制标题
跨组学通路分析表明，eQTL 通过调节细胞凋亡通路表达，促进大骨节病软骨细胞凋亡。
DOI：
10.1016/j.gene.2014.10.018
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发表时间：
2014-12
期刊：
影响因子：
3.5
通讯作者：
Deng, Hongwen
中科院分区：
文献类型：
--
作者：
Zhang, Feng;Wen, Yan;Guo, Xiong;Yang, Tielin;Shen, Hui;Chen, Xiangding;Tan, Lijun;Tian, Qing;Deng, Hongwen
大骨节病是一种严重的骨关节病，主要表现为软骨细胞过度坏死和凋亡。大骨节病软骨细胞过度凋亡的分子信号通路尚不清楚，导致目前缺乏有效的医学干预措施。阐明表达数量性状基因座（expression quantitative trait loci，eQTLs）是否通过调控凋亡途径的表达而参与大骨节病软骨细胞过度凋亡。本研究利用AffysseHuman SNP Array 6.0对1717名中国汉族人群进行了大骨节病全基因组eQTLs通路关联分析。采用PLINK软件进行大骨节病全基因组关联分析。基于GWAS结果，采用改进的基因集富集算法进行通路关联分析。将大骨节病相关通路与大骨节病关节软骨中异常表达的通路进行比较，通过大骨节病的微阵列研究鉴定。我们鉴定了4条eQTL通路，它们不仅与大骨节病显著相关，而且在大骨节病关节软骨中异常表达，包括REACTOME_INTRINSIC_PATHWAY_FOR_APOPTOSIS（P= 0.008）、MAHAJAN _RESPONSE_TO_IL1A_UP（P= 0.010）、KEGG_PEROXISOME（P= 0.005）和MARKS_HDAC_TARGETS_UP（P= 0.006）。这些结果表明，eQTL通过调控凋亡相关通路的表达，参与了大骨节病软骨细胞的过度凋亡。这项研究为大骨节病的遗传易感性和治疗原理提供了新的见解。
Kashin–Beck disease (KBD) is a serious osteoarthropathia, mainly characterized by excessive chondrocyte necrosis and apoptosis. The molecular signaling pathways underlying KBD excessive chondrocyte apoptosis remain unclear, leading to a lack of effective medical interventions now. To clarify whether expression quantitative trait loci (eQTLs) contribute to excessive chondrocyte apoptosis of Kashin–Beck disease through regulating the expression of apoptosis pathways. We conducted a genome-wide eQTLs based pathway association analysis of KBD using Affymetrix Human SNP Array 6.0 in 1717 Chinese Han subjects. PLINK software was used for genome-wide association study (GWAS) of KBD. A modified gene set enrichment algorithm was applied for pathway association analysis based on GWAS results. The KBD-associated pathways were compared with abnormally expressed pathways in KBD articular cartilage, identified by microarray study of KBD. We identified 4 eQTLs pathways, which were not only significantly associated with KBD, but also abnormally expressed in KBD articular cartilage, including REACTOME_INTRINSIC_PATHWAY_FOR_APOPTOSIS (P= 0.008), MAHAJAN _RESPONSE_TO_IL1A_UP (P= 0.010), KEGG_PEROXISOME (P= 0.005) and MARKS_HDAC_TARGETS_UP (P= 0.006). Our results suggest that eQTLs contributed to KBD excessive chondrocyte apoptosis through regulating the expression of apoptosis related pathways. This study provides novel insight into the genetic susceptibility and therapeutic rationale of KBD.
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