GPNMB contributes to a vicious circle for chronic obstructive pulmonary disease

Osteoporosis (OP) is significant and debilitating comorbidity of chronic obstructive pulmonary disease (COPD). We hypothesize that genetic variance identified with OP may also play roles in COPD. We have conducted a large-scale relation data analysis to explore the genes implicated with either OP or COPD, or both. Each gene linked to OP but not to COPD was further explored in a mega-analysis and partial mega-analysis of 15 independently collected COPD RNA expression datasets, followed by gene set enrichment analysis (GSEA) and literature-based pathway analysis to explore their functional linked to COPD. A multiple linear regression (MLR) model was built to study the possible influence of sample size, population region, and study date on the gene expression data in COPD. At the first step of the analysis, we have identified 918 genes associated with COPD, 581 with OP, and a significant overlap (P<2.30e-140; 210 overlapped genes). Partial mega-analysis showed that, one OP gene, GPNMB presented significantly increased expression in COPD patients (P-value = 0.0018; log fold change = 0.83). GPNMB was enriched in multiple COPD pathways and plays roles as a gene hub formulating multiple vicious COPD pathways included gene MMP9 and MYC. GPNMB could be a novel gene that plays roles in both COPD and OP. Partial mega-analysis is valuable in identify case-specific genes for COPD.