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

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.

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.

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.

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.