Identification of susceptibility genes for osteoporosis through interaction between smoking and genetic factors / 西安交通大学学报(医学版)

ABSTRACT

Objective To make a systematic analysis of the interaction between osteoporosis and smoking to elucidate the molecular mechanisms underlying osteoporosis susceptibility affected by smoking.Methods First,a two-way ANOVA analysis was conducted using microarray data to search all potential genes associated with both smoking and osteoporosis.We further explored the potential biologically related metabolic pathways through gene pathway enrichment analysis.Then the interaction genes within enriched pathways were verified by genome-wide gene-environment interaction analysis.Finally,protein-protein interaction analysis was applied to identify the core regulatory network in which those verified genes involved.Results We identified 441 risk genes closely associated with both smoking and osteoporosis by microarray analysis.Through gene pathway analysis,we identified a vital metabolism pathway, gap junction, which is a potential mediator between smoking and osteoporosis process. Finally,we verified some critical genes by genome-wide gene-environment interaction analysis,and revealed a potential smoking-osteoporosis interaction core regulatory network that included 1 3 proteins by protein network analysis.Conclusion We have discovered a new regulatory framework connecting smoking and osteoporosis, which provides new clues about disease etiologies and novel promising drug targets.