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Trans-omics pathway analysis suggests that eQTLs contribute to chondrocyte apoptosis of Kashin-Beck disease through regulating apoptosis pathway expression.
Gene. 2014 Dec 15; 553(2):166-9.GENE

Abstract

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.

Authors+Show Affiliations

Key Laboratory of Environment and Gene Related Diseases of Ministry Education, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, PR China.Key Laboratory of Environment and Gene Related Diseases of Ministry Education, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, PR China.Key Laboratory of Environment and Gene Related Diseases of Ministry Education, School of Public Health, Health Science Center, Xi'an Jiaotong University, Xi'an, PR China. Electronic address: guox@mail.xjtu.edu.cn.Key Laboratory of Biomedical Information Engineering of Ministry of Education, and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, PR China.Department of Biostatistics and Bioinformatics, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA; Center for Bioinformatics and Genomics, Tulane University, New Orleans, LA, USA.Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha, PR China.Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha, PR China.Department of Biostatistics and Bioinformatics, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA; Center for Bioinformatics and Genomics, Tulane University, New Orleans, LA, USA.Department of Biostatistics and Bioinformatics, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA; Center for Bioinformatics and Genomics, Tulane University, New Orleans, LA, USA.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25307768

Citation

Zhang, Feng, et al. "Trans-omics Pathway Analysis Suggests That eQTLs Contribute to Chondrocyte Apoptosis of Kashin-Beck Disease Through Regulating Apoptosis Pathway Expression." Gene, vol. 553, no. 2, 2014, pp. 166-9.
Zhang F, Wen Y, Guo X, et al. Trans-omics pathway analysis suggests that eQTLs contribute to chondrocyte apoptosis of Kashin-Beck disease through regulating apoptosis pathway expression. Gene. 2014;553(2):166-9.
Zhang, F., Wen, Y., Guo, X., Yang, T., Shen, H., Chen, X., Tan, L., Tian, Q., & Deng, H. W. (2014). Trans-omics pathway analysis suggests that eQTLs contribute to chondrocyte apoptosis of Kashin-Beck disease through regulating apoptosis pathway expression. Gene, 553(2), 166-9. https://doi.org/10.1016/j.gene.2014.10.018
Zhang F, et al. Trans-omics Pathway Analysis Suggests That eQTLs Contribute to Chondrocyte Apoptosis of Kashin-Beck Disease Through Regulating Apoptosis Pathway Expression. Gene. 2014 Dec 15;553(2):166-9. PubMed PMID: 25307768.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Trans-omics pathway analysis suggests that eQTLs contribute to chondrocyte apoptosis of Kashin-Beck disease through regulating apoptosis pathway expression. AU - Zhang,Feng, AU - Wen,Yan, AU - Guo,Xiong, AU - Yang,Tielin, AU - Shen,Hui, AU - Chen,Xiangding, AU - Tan,Lijun, AU - Tian,Qing, AU - Deng,Hong-Wen, Y1 - 2014/10/11/ PY - 2014/06/18/received PY - 2014/08/18/revised PY - 2014/10/08/accepted PY - 2014/10/14/entrez PY - 2014/10/14/pubmed PY - 2015/2/3/medline KW - Apoptosis KW - Expression quantitative trait loci KW - Kashin–Beck disease KW - Pathway SP - 166 EP - 9 JF - Gene JO - Gene VL - 553 IS - 2 N2 - 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. SN - 1879-0038 UR - https://www.unboundmedicine.com/medline/citation/25307768/Trans_omics_pathway_analysis_suggests_that_eQTLs_contribute_to_chondrocyte_apoptosis_of_Kashin_Beck_disease_through_regulating_apoptosis_pathway_expression_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-1119(14)01152-4 DB - PRIME DP - Unbound Medicine ER -