Fig. 1.

Identifying candidate COPD genes through genomic and functional approaches. WES in 62 highly susceptible smokers and 30 exceptionally resistant smokers were conducted to identify exonic variants that may contribute to disease risk or resistance to CS. Top scoring candidate genes from the rare variant and gene set analyses were further filtered by requiring that the gene be expressed in primary HBECs, and 81 candidate genes were selected for in vitro functional testing in CSE-exposed HBECs. Using siRNA-mediated gene silencing experiments, we identified candidate genes whose knockdown augmented CSE-induced cytotoxicity, protected CSE-induced cytotoxicity, or alone-reduced cell viability