Thus, our main goal was to identify the gene–environment interaction of childhood ETS exposure with IL1RN variants and asthma risk and evaluate the impact of GEI on the risk of asthma and early onset asthma to bridge the knowledge gap in understanding the seemingly diverging effects of some rare IL1RN genotypes on asthma susceptibility, in contrast to haplotype-based findings in existing cohort studies. Here, IL1RN is linked to asthma.