Separating the effects of childhood- and adult-onset asthma on rheumatoid arthritis and systemic lupus erythematosus: a Mendelian randomization study

Abstract Background : The causal relationship between asthma and rheumatoid arthritis (RA) has not been well investigated from a perspective of genetics. This study investigated the effects of asthma appearing at different ages on the risk of RA and systemic lupus erythematosus (SLE) using the Mendelian randomization (MR) method. Methods : Single nucleotide polymorphisms associated with asthma were used as instrumental variables. The inverse-variance weighted (IVW) method was used as the main MR method to estimate causal effects based on the summary-level data for RA and SLE. Cochran’s Q test as the sensitivity analyses validated the robustness of the results and ensured the absence of heterogeneity and horizontal pleiotropy. Results : Asthma (adult onset) and asthma (childhood onset) were identified to be causally associated with RA based on the IVW method (adult-onset asthma, odds ratio [OR]: 1.360, 95% confidence interval [CI]: 1.176–1.572, p = 3.30×10 -5 ; childhood-onset asthma, OR: 1.119, 95% CI: 1.030–1.216, p = 7.96×10 -3 ). There were no associations between genetically predicted asthma (both adult and childhood onset) and the risk of SLE. Sensitivity analysis, like Cochran’s Q test, further excluded the influence of heterogeneity and horizontal pleiotropy. Conclusions : Both adult- and childhood-onset asthma were causally associated with RA but not SLE. The findings are valuable for understanding inflammation related to asthma and RA pathology and can guide the prevention of different diseases.