Gene-Air Pollution Interaction and Diversity of Genetic Sampling: The Southern California Children's Health Study

Gene-environment interactions have been observed for childhood asthma, however few have been assessed in ethnically diverse populations. Thus, we examined how polygenic risk score (PRS) modifies the association between ambient air pollution exposure (nitrogen dioxide [NO₂], ozone, particulate matter < 2.5 and < 10 μm) and childhood asthma incidence in a diverse cohort. Participants (n = 1794) were drawn from the Southern California Children's Health Study, a multi-wave prospective cohort followed from 4th to 12th grade. PRS was developed using single nucleotide polymorphisms previously associated with childhood asthma. PRS-asthma associations and PRS-air pollutant interactions were estimated using Poisson regression. An interquartile range PRS increase was associated with 36% (95% CI: 9%, 70%) higher asthma incidence among non-Hispanic children, but not associated with asthma among Hispanic children (rate ratio: 0.81 [95% CI: 0.62, 1.04]). NO₂-PRS interaction was borderline significant in the overall sample (coefficient: 0.23 [95% CI: -0.03, 0.49]). Limited evidence was observed for a positive interaction between PRS and NO₂ exposure associated with asthma incidence; however, the literature-based PRS was not associated with asthma among Hispanic participants. Equitable, diverse genetic sampling approaches are needed to better identify clinically relevant SNPs in this population.