Trans-omics pathway analysis suggests that eQTLs contribute to chondrocyte apoptosis of Kashin-Beck disease through regulating apoptosis pathway expression

Feng Zhang; Yan Wen; Xiong Guo; Tielin Yang; Hui Shen; Xiangding Chen; Lijun Tan; Qing Tian; Hong-Wen Deng

doi:10.1016/j.gene.2014.10.018

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. doi: 10.1016/j.gene.2014.10.018. Epub 2014 Oct 11.

Authors

Feng Zhang¹, Yan Wen¹, Xiong Guo², Tielin Yang³, Hui Shen⁴, Xiangding Chen⁵, Lijun Tan⁵, Qing Tian⁴, Hong-Wen Deng⁴

Affiliations

¹ 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.
² 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.
³ 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.
⁴ 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.
⁵ Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha, PR China.

PMID: 25307768
DOI: 10.1016/j.gene.2014.10.018

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.

Keywords: Apoptosis; Expression quantitative trait loci; Kashin–Beck disease; Pathway.

Publication types

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

MeSH terms

Adult
Apoptosis*
Chondrocytes / cytology*
Female
Humans
Kashin-Beck Disease / genetics*
Male
Middle Aged
Oligonucleotide Array Sequence Analysis
Quantitative Trait Loci*
Transcriptome*