Genetic susceptibility to asthma increases the vulnerability to indoor air pollution

Introduction Indoor air pollution and maternal smoking during pregnancy are associated with respiratory symptoms in infants, but little is known about the direct association with lung function or interactions with genetic risk factors. We examined associations of indoor particulate matter of diameter ≤10 µm (PM₁₀) exposure and maternal smoking with infant lung function and the role of gene-environment interactions.

Methods Data from the Drakenstein Child Health Study, a South African birth cohort, were analysed (N=270). Lung function was measured at 6 weeks and 1 year of age and lower respiratory tract illness (LRTI) episodes were documented. We measured prenatal and postnatal PM₁₀ exposures using devices placed in homes and prenatal tobacco smoke exposure using maternal urine cotinine levels. Genetic risk scores (GRS) determined from associations with childhood-onset asthma (COA) in the UK Biobank were used to investigate effect modifications.

Results Pre- and postnatal exposure to PM₁₀ as well as maternal smoking during pregnancy were associated with reduced lung function at 6 weeks and 1 year as well as LRTI in the first year. Due to a significant interaction between the GRS and prenatal exposure to PM₁₀, infants carrying more COA-risk alleles were more susceptible to PM₁₀-associated reduced lung function (p-interaction=0.007). This interaction was stronger in infants with black African ancestry (p-interaction=0.001) and non-existent in children with mixed ancestry (p-interaction=0.876).

Conclusions PM₁₀ and maternal smoking exposures were associated with reduced lung function, with a higher susceptibility for infants with an adverse genetic predisposition for asthma that also depended on the infant's ancestry.