Follow-up on genome-wide main effects: Do polymorphisms modify the air pollution effect on lung function decline in adults?

Improved air quality has been found associated with attenuated age-related decline in lung function. But whether genetic polymorphisms strongly associated with lung function play a modifying role in this attenuation process has so far not been investigated.We selected ten single nucleotide polymorphisms derived from the largest genome-wide association studies on lung function and examined whether they modified the association between the change in exposure to particulate matter ≤10 μm (ΔPM10) and lung function decline. 4310 participants from the SAPALDIA cohort provided valid spirometry measurements, a detailed pulmonary health questionnaire both at baseline and 11 years later as well as blood samples for genetic testing. Spatially and temporally resolved air pollution exposures were assigned on an individual level based on participants' residences.Statistically significant interactions of moderate strength with ΔPM10 were detected for rs2284746. Individuals with the CC genotype had a 21 ml slower annual decline of the mid expiratory flow per 10 μg/m3 PM10 reduction over an 10-year period, while the benefits of CG and GG carriers were smaller (14 and 7 ml per year, respectively; Pinteraction = 0.04). The attenuated annual decline in the percentage of the forced expiratory volume in one second relative to the forced vital capacity (FEV1/FVC) was also increased with the presence of each C-allele (Pinteraction = 0.009). We observed further suggestive interactions of similar magnitude in never-smokers, but none of the results would remain statistically significant after correction for multiple testing.We could not find strong evidence that lung function benefits from improved air quality are modified by polymorphisms associated with lung function level in large meta-analyzed genome-wide association studies. Keywords: Air pollution, Lung function, Genetic polymorphism, Gene–environment interaction