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

• We conducted a trans-omics pathway analysis of KBD.
• 4 KBD associated pathways were abnormally expressed in KBD articular cartilage.
• eQTL contributed to KBD chondrocyte apoptosis through regulating apoptosis pathway.
• Integrating pathway association and expression analysis performed well.

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.