Incidence and Genetic Risk of Juvenile Idiopathic Arthritis in Norway by Latitude

Abstract

Objective: We aimed to investigate the incidence of juvenile idiopathic arthritis (JIA) in the three geographic regions of Norway and whether potential regional incidence differences are explained by environmental or genetic factors across regions.

Methods: We conducted a register-based cohort study including all Norwegian children born from 2004 to 2019, with follow-up throughout 2020. The JIA diagnosis, defined by at least two International Classification of Diseases, Tenth Revision codes for JIA, was validated against medical records. The incidence rate (IR) and hazard ratio (HR) for JIA were estimated for all Norway and for the North, Mid, and South regions. In a subsample from the Norwegian Mother, Father, and Child Cohort Study (MoBa), the genetic risk for JIA was assessed in the three regions.

Results: After median 9.1 (range 0.3-16.0) years of follow-up, we identified 1,184 patients with JIA and 910,058 controls. The IR for JIA/100,000 person-years was 14.4 in all of Norway, 25.9 in the North region, 17.9 in the Mid region, and 12.5 in the South region. The HR (95% confidence interval [CI]) of JIA in the North region was 2.07 (1.77-2.43) and in the Mid region HR 1.43 (95% CI 1.23-1.67) compared with the South region. Adjustments for perinatal factors, socioeconomic status, and early antibiotic exposure did not change our estimates substantially. In MoBa (238 patients with JIA, 57,392 controls), the association between JIA and region of birth was no longer significant when adjusting for genetic factors.

Conclusion: We found a higher incidence of JIA with increasing latitude without evidence for available environmental factors explaining the observed gradient. In contrast, genetic factors modified the association, but further studies are warranted.

Figure 1

IR of JIA by region of birth in the Medical Birth Registry of Norway sample. CI, confidence interval; IR, incidence rate; JIA, juvenile idiopathic arthritis.

Figure 2

Associations between region of birth and JIA in the Norwegian Mother, Father, and Child Cohort Study sample. CI, confidence interval; JIA, juvenile idiopathic arthritis. Color figure can be viewed in the online issue, which is available at http://onlinelibrary.wiley.com/doi/10.1002/art.43040/abstract.