Increased risk of rheumatoid arthritis in patients with asthma: a genetic association study using two-sample Mendelian randomization analysis.

Abstract

Observational studies have explored the association between asthma and some types of arthritis, including rheumatoid arthritis and osteoarthritis, but the results are largely contradictory. We aimed to investigate the causal effects of asthma on arthritis including osteoarthritis, rheumatoid arthritis, gout and ankylosing spondylitis. Two-sample Mendelian randomization (MR) analysis was used to investigate the causal effects of asthma on each arthritis. The genetic instruments for asthma were obtained from a large genome-wide association study of asthma. Inverse-variance weighted (IVW) method was used as the main analysis of MR. Bonferroni-adjusted P value threshold was used to account for multiple comparisons. MR-IVW analysis suggested that adult-onset asthma (AOA) was associated with increased risk of rheumatoid arthritis. The odds ratio for rheumatoid arthritis associated with AOA and childhood-onset asthma (COA) were 1.018 (95% CI, 1.011 to 1.025; P < 0.001) and 1.006 (95% CI, 1.001 to 1.012; P=0.046), respectively. For osteoarthritis, gout, or ankylosing spondylitis, all the MR analyses showed no significant causal effects of AOA or COA on them. We also performed a reverse MR analysis to explore the causal effects of rheumatoid on all asthma, allergic asthma or non-allergic asthma, and found no significant causal effects on them. Genetically predicted AOA predisposes patients to an increased risk of rheumatoid arthritis, but has no causal effects on osteoarthritis, gout, and ankylosing spondylitis. The result of COA on rheumatoid arthritis is suggestive of potential causal relationship but needs to be confirmed in further studies.