The Causal Associations Between Juvenile Idiopathic Arthritis and 15 Mental Disorders: A Two-Sample Mendelian Randomization Study

Abstract

Abstract Background: This study explored causal associations between juvenile idiopathic arthritis (JIA) and 15 common mental disorders. Method: Two-sample Mendelian Randomization (MR) was used in this study; JIA was regarded as exposure, and 15 mental disorders were regarded as outcomes. All data were obtained from the 8th FinnGen Genome-wide association studies (GWAS) summary statistics. Inverse-variance weighted (IVW), MR-Egger regression, weight median, simple mode, and weight mode methods were used to estimate causal associations. The Cochrane Q test, Egger-intercept test, Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO), and leave-one-out tests were performed to test heterogeneity, horizontal pleiotropy, and sensitivity of the results. Result: IVW showed that JIA was an independent risk factor for autism (OR:1.179, 95%CI:1.031-1.348, P=0.016), bipolar disorder (OR:1.057, 95%CI:1.018-1.098, P=0.004), and depression (OR:1.025, 95%CI:1.009-1.041, P=0.002); it also showed that JIA was inversely associated with bulimia nervosa (OR:0.854, 95%CI:0.781-0.932, P=4.4×10-4). JIA did not affect the other 11 mental disorders. The sensitivity test showed that horizontal pleiotropy and heterogeneity did not exist (p>0.05). The reliability of the associations was tested using a leave-one-out test. Conclusion: This study shows that JIA is associated with the risk of some mental disorders. It can provide genetic evidence for the early detection of mental disorders in children with JIA. Furthermore, it also provides a theoretical basis for the comprehensive treatment of patients with JIA.