Genome-wide association studies (GWAS) and meta-analyses, have linked COPD to a locus on chromosome 15q25. This was explored in a mouse model of cigarette smoke–induced bronchitis and emphysema. 15q25 also encompasses three genes, CHRNA3, CHRNA5, and CHRNB4, coding for the α3, α5, and β4 subunits of the nicotinic acetylcholine receptor (nAChR). This locus has been previously linked to tobacco smoking and nicotine consumption, using GWAS, validated in our transgenic mouse and rat models for increased nicotine intake and relapse. However, it was unclear whether the associations between SNPs and COPD are solely due to smoking. It is also important to note that a substantial percentage of COPD patients are exposed to biomass fuel-derived smoke, and to unidentified causes. Moreover, the non-synonymous SNP rs16969968 (α5SNP) has been linked to lung cancer, a major comorbidity associated with COPD.

Importantly, two GWAS identified a potential innate, smoking-independent component of the disease, in carriers of the nicotinic receptor SNPs. Specifically, at equal smoking levels, subjects carrying the SNP were significantly more prone to develop the disease. In this latest work, the researchers studied the role of α5SNP in the remodeling of the airways and inflammation, independently of its established role in nicotine dependence.