Urticaria and increased risk of rheumatoid arthritis: a two-sample Mendelian randomisation study in European population

Abstract

ABSTRACT Background In recent years, a growing body of observational studies suggest that urticaria is associated with a higher risk of rheumatoid arthritis (RA). However, the causal association between urticaria and RA remains unknown. Objective To investigate the causal relationship of urticaria and RA in European populations by Mendelian randomisation (MR) approach. Methods We conducted two-sample MR analyses. Eleven single-nucleotide polymorphisms associated with urticaria were used as instrumental variables. The summary data on urticaria were derived from FinnGen Data Freeze 2. The summary data on RA were obtained from a published meta-analysis using European samples. Four MR methods were applied to the MR estimates. Three heterogeneity tests, including Cochran’s Q test, single variant analysis, and leave-one-out variant analysis, were used. The pleiotropy and horizontal pleiotropy among instrumental variables were assessed with MR-Egger regression intercept, MR pleiotropy residual sum and outlier global test, and PhenoScanner. Results The MR analysis suggested that urticaria was causally associated with RA (odds ratio = 1.114, 95% confidence interval = 1.024–1.211, p = .011). No genetic pleiotropy or horizontal pleiotropy was revealed by MR-Egger regression intercept and MR pleiotropy residual sum and outlier global test. The sensitivity analysis results were relatively robust. Conclusions The MR analysis suggested there was sufficient evidence to indicate urticaria is the cause of RA.