Abstract
Objective: Osteomyelitis (OM) is an acute or chronic inflammatory process, characterized by severe inflammation and progressive bone destruction. Limited efforts have been made to explore the genetic basis of OM.Method: The genome-wide association study data set of OM was obtained from the UK Biobank. A transcriptome-wide association study (TWAS) of OM was conducted by the FUSION tool using the gene expression reference weights of lymphocytes and blood. The OM-associated genes identified by TWAS were subjected to gene ontology (GO) enrichment analysis to explore OM-related gene sets. The TWAS results of OM were finally compared with a genome-wide mRNA expression profiling of OM to detect common genes and gene sets.Results: TWAS of OM detected 86 genes for lymphocytes and 387 genes for blood. Comparing the genes identified by TWAS and mRNA expression profiling detected eight common genes for OM, including VWF (pTWAS = 0.0030, pmRNA = 3.44 × 10−9), CCDC50 (pTWAS = 0.0130, pmRNA = 0.0003), and TPD52 (pTWAS = 0.0180, pmRNA = 1 × 10−6). GO analysis of the genes identified by TWAS detected multiple OM-associated GO terms, e.g. peroxisomal matrix (pTWAS = 0.0082), extracellular exosome (pTWAS = 0.0248), and monooxygenase activity (pTWAS = 0.0040). Further comparing the GO results of TWAS and mRNA expression profiling detected one common GO term, named extracellular exosome (pTWAS = 0.0248, pmRNA = 0.0027).Conclusion: This integrative study of TWAS and mRNA expression profiling detected multiple candidate genes and GO terms for OM. Our results provide novel clues for understanding the pathogenesis of OM.
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