title: Trans-omics pathway analysis suggests that eQTLs contribute to chondrocyte apoptosis of Kashin-Beck disease through regulating apoptosis pathway expression.
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.affiliation: 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.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wen
authors.affiliation: 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.
authors.forename: Xiong
authors.initials: X
authors.lastname: Guo
authors.affiliation: 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.
authors.forename: Tielin
authors.initials: T
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Hui
authors.initials: H
authors.lastname: Shen
authors.affiliation: Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha, PR China.
authors.forename: Xiangding
authors.initials: X
authors.lastname: Chen
authors.affiliation: Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha, PR China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Tan
authors.affiliation: 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.
authors.forename: Qing
authors.initials: Q
authors.lastname: Tian
authors.affiliation: 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.
authors.forename: Hong-Wen
authors.initials: HW
authors.lastname: Deng
mesh_terms: D000328:Adult; D017209:Apoptosis; D019902:Chondrocytes / Q000166:cytology*; D005260:Female; D006801:Humans; D057767:Kashin-Beck Disease / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D040641:Quantitative Trait Loci; D059467:Transcriptome
keywords: Apoptosis; Expression quantitative trait loci; Kashin–Beck disease; Pathway