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| Pathway expression analysis is a powerful tool for pathogenetic studies of complex diseases. Kashin-Beck disease (KBD) is a serious osteoarthropathia, mainly characterized by excessive chondrocyte necrosis and apoptosis. To improve the performance of pathway expression analysis, we proposed a trans-omics expression quantitative trait loci (eQTLs) -weighted pathway expression analysis (EPEA) approach for trans-omics joint analysis of genome-wide microarray and eQTLs data. In EPEA, expression quantitative trait loci (eQTLs)-weighted Kolmogorov-Smirnov-like running sum statistic was applied for pathway enrichment analysis. Permutations are used to evaluate the significance of statistics. Using the real genome-wide microarray and eQTLs data of KBD, EPEA identified 4 apoptosis-related pathways significantly associated with KBD, including SA_PROGRAMMED_CELL_DEATH (P value = 3.7×10-3), BIOCARTA_ MITOCHONDRIA_PATHWAY (P value = 4.4×10-3), REACTOME_INTRINSIC_ PATHWAY_FOR_APOPTOSIS (P value = 6.4×10-3), ST_FAS_ SIGNALING_PATHWAY (P value = 8.9×10-3). Our results provided novel insight into the molecular mechanism underlying the excessive chondrocyte apoptosis of KBD, and illustrated the application of EPEA for joint pathway analysis of microarray and eQTLs data. A program, named EPEA was developed to implement the proposed approach. ????? |
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| Keywords:expression quantitative trait loci, pathway, trans-omics analysis |
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