结合吸烟与遗传因素交互作用鉴定骨质疏松症易感基因

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 13 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.