Twinship and Childhood Atopic Disease: Understanding Early-Life Factors Among Discordant Twins in Ontario, Canada

Abstract

Background: Parents often question why one of their children 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 aims to investigate potential risk factors that modifies the risk of asthma and other atopic diseases between twins in shared early-life environments. Methods: 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 (asthma, allergic rhinitis, and eczema) and early-life factors. Results: This study included 24,392 twin-pairs from Ontario Canada aged 1 to 15 years. 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 were 69% (95% CI: 1·54-1·84) and 35% (95% CI: 1·23-1·49) higher odds to have asthma discordance, respectively. Twins who were delivered by Caesarian-section 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), and is strongly suggested for eczema discordance (aOR: 1·05, 95% CI: 1·00-1·12), compared to pairs who had vaginal births. Conclusion: This population-based study found associations of various early-life factors and asthma and allergic diseases discordance between twins. While early-life factors were associated with disease risks in children, genetic factors played a strong underlying role. Funding: This study was funded by the Asthma and COPD Program, Ontario Ministry of Health and Long-Term Care (MOHLTC). Declaration of Interest: None to declare. Ethical Approval: Ethics approval for this study was obtained from the Hospital for Sick Children Research Ethics Board in Toronto, Ontario.