SMAD3 and chronic obstructive pulmonary disease: In summary, we have used an in silico validation analysis to corroborate the involvement of SPP1, APOA1, CTSD, TIMP1, RXFP1, and SMAD3 as causal or upstream genes that may drive the cell transcriptomics to a status similar to or contrasting with COPD, suggesting their potential as therapeutic targets for intervention.