A Tale of Many Canadas: Associations of Ancestry With Juvenile Idiopathic Arthritis Categories and Disease Severity at Presentation to Care

OBJECTIVE: To assess associations of ancestry with juvenile idiopathic arthritis (JIA) categories and clinical Juvenile Arthritis Disease Activity Scores (cJADAS10) at presentation to pediatric rheumatology care in a multicultural country with universal health care. METHODS: Parents reported their child's ancestry in the Research in Arthritis in Canadian Children Emphasizing Outcomes (ReACCh-Out) cohort. For each ancestry reported for ≥30 children, we compared JIA category distribution and median cJADAS10 scores among three groups: only that ancestry, with that and other ancestries, and without that ancestry. Chi-square, Fisher's exact, and Kruskal-Wallis tests compared the three groups and multivariable linear regression assessed factors associated with cJADAS10 scores. RESULTS: Among 1,407 participants, 629 (44.7%) reported more than one ancestry. British ancestry was associated with higher median cJADAS10 scores (7.5) and higher frequency of enthesitis-related arthritis (18.7%) and psoriatic arthritis (10.0%), French ancestry was associated with lower cJADAS10 scores (5.8) and higher oligoarthritis (51.2%), Indigenous ancestry was associated with higher cJADAS10 scores (11.0) and higher rheumatoid factor-positive polyarthritis (21.9%), Black ancestry was associated with higher rheumatoid factor-positive polyarthritis (16.0%), and Eastern European ancestry was associated with lower cJADAS10 scores (3.6). Associations of ancestry with cJADAS10 scores were largely explained by differences in JIA categories (total R² = 0.28, with R² = 0.25 for JIA category alone). Black ancestry was associated with longer time from symptom onset to diagnosis (27 vs 18.9 weeks). CONCLUSIONS: British and French ancestries had distinct associations with JIA categories and cJADAS10 scores, and many children had multiple ancestries, questioning the use of a single "European" reference group. Higher cJADAS10 scores were largely explained by differences in JIA categories across ancestries.