Asthma and atopic dermatitis as risk factors for rheumatoid arthritis: a bidirectional mendelian randomization study

Abstract

Background: Previous observational studies have shown an association between asthma, atopic dermatitis (AD) and rheumatoid arthritis (RA). However, the bidirectional cause-effect chain between asthma and AD and RA has not been proven yet. Methods: We performed bidirectional two-sample Mendelian randomization (TSMR) and selected single nucleotide polymorphisms (SNPs) associated with asthma, AD, and RA as instrumental variables. All of the SNPs were obtained from the latest genome-wide association study in Europeans. Inverse variance weighted (IVW) was the main method used in MR analysis. MR-Egger, weighted model, simple model, and weighted median were used for quality control. The robustness of the results was tested by sensitivity analysis. Results: Asthma was found to be the largest effect size for RA susceptibility using the IVW method (OR, 1.35;95%CI, 1.13–1.60; P, 0.001), followed by AD (OR, 1.10;95%CI, 1.02–1.19; P, 0.019). In contrast, there was no causal relationship between RA and asthma (IVW: P = 0.673) or AD (IVW: P = 0.342). No pleiotropy or heterogeneity was found in the sensitivity analysis. Conclusion: Findings from this study showed a causal relationship between genetic susceptibility to asthma or AD and increased risk of RA, but do not support a causal relationship between genetic susceptibility to RA and asthma or AD.