Twinship and childhood atopic disease: understanding early-life factors among discordant twins

Parents often question why one of their children would have asthma while their siblings do not. With twins, this is especially perplexing. The gene-environment interaction hypothesis suggests that early-life environmental exposures interact with genes, leading to asthma and atopic diseases. This study sought to investigate twins for potential early-life risk factors that modify the risk of asthma, allergic rhinitis, and eczema. A paired population-based open cohort study was conducted using health administrative data between April 1, 2004 and March 31, 2019 from Ontario, Canada. The study population consisted of Ontario twins born between 2004-2017. Multivariable logistic regression was used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI) for associations between discordance of allergic conditions and early-life factors. 24,392 twin-pairs from Ontario Canada aged 1 to 15 years were included. 15.7%, 17.9%, and 31.9% of twin-pairs had discordant asthma, allergic rhinitis, and eczema, respectively. Compared to female-female twin-pairs, male-female and male-male twin pairs had 69% (95% CI:1.54-1.84) and 35% (95% CI:1.23-1.49) higher odds of asthma discordance, respectively. Twins delivered by Caesarean-section, compared to vaginal deliveries, had significantly higher odds of asthma (aOR:1.09, 95% CI:1.01-1.18) and allergic rhinitis (aOR:1.11, 95% CI:1.04 1.20), while associations were strongly suggested for eczema discordance (aOR:1.05, 95% CI:1.00-1.12). This population-based study found associations of various early-life factors and discordances of asthma, allergic rhinitis, and eczema between twins, though we lacked data for control of zygosity and variance. While early-life factors were associated with disease risks in children, other factors played an underlying role.