Genome-wide gene-air pollution interaction analysis of lung function in 300,000 individuals

Abstract

AbstractImpaired lung function is predictive of mortality and is a key component in the diagnosis of chronic obstructive pulmonary disease. Lung function has a strong genetic component but is also affected by environmental factors such as increased exposure to air pollution. How genetic factors and air pollution interact to affect lung function is however less understood.We conducted a genome-wide gene-air pollution interaction analysis of spirometry measures with three measures of air pollution at home address: particulate matter (PM2.5 & PM10) and nitrogen dioxide (NO2), in approximately 300,000 unrelated European individuals from UK Biobank. We explored air pollution interactions with previously identified lung function signals and determined their combined interaction effect using a polygenic risk score (PRS).We identified seven genome-wide interaction signals (P < 5 × 10−8), and a further ten suggestive interaction signals (P < 5 × 10−7). We found statistical evidence of interaction with PM2.5 for previous lung function signal, rs10841302, near AEBP2, suggesting increased susceptibility of FEV1/FVC to PM2.5, as copies of the G allele increased (interaction beta: −0.073 percentage points, 95%CI: −0.105, −0.041). There was no observed interaction between air pollutants and the weighted genetic risk score.We carried out the largest genome-wide gene-air pollution interaction study of lung function and identified effects of clinically relevant size and significance. We observed up to 440ml lower lung function for certain genotypes associated with mean levels of outdoor air pollution at baseline, which is approximately equivalent to nine years of normal loss of lung function.