The causal effect of juvenile idiopathic arthritis on IgA nephropathy: A Mendelian randomization study

IgA nephropathy (IgAN) has been documented in patients with various comorbidities. Previous observational studies showed an association between juvenile idiopathic arthritis (JIA) and IgAN. The aim of this study was to determine whether there is a causal effect of JIA on the risk of IgAN using a 2-sample Mendelian randomization (MR) approach. A 2-sample MR analysis was conducted to elucidate the potential causal relationship between JIA and IgAN. Summary-level data from genome-wide association studies in the European population were utilized, including IgAN (5556 cases and 21,178 controls) and JIA (3305 cases and 9196 controls). The inverse variance weighted method showed significant evidence of a positive causal relationship between genetically predicted JIA and IgAN. For each standard deviation increase in genetically predicted JIA, the risk of IgAN was found to be increased by 22% (odds ratio [OR] = 1.22, 95% CI: 1.10–1.29, P  = 3.03 × 10 ⁻⁴ ). Similar associations were observed with the weighted median (OR: 1.16, 95% CI: 1.05–1.29) and weighted mode methods (OR: 1.16 95% CI: 1.02–1.33), but not with the simple median (OR: 1.22, 95% CI: 0.99–1.50) and MR Egger method (OR: 1.21, 95% CI: 0.93–1.57). Reverse MR analysis found no inverse causal relationship between these 2 diseases. This study provides genetic evidence supporting a causal link between JIA and an increased risk of IgAN. In JIA patients, periodic evaluation of kidney function and proteinuria is warranted.