Examining Health Outcomes in Juvenile Idiopathic Arthritis: A Genetic Epidemiology Study

Sarah L N Clarke*, Rebecca Richmond, Jie Zheng, Wes Spiller, Athimalaipet V Ramanan, Gemma C Sharp, Caroline L Relton

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

2 Citations (Scopus)
87 Downloads (Pure)

Abstract

Objective

Juvenile idiopathic arthritis (JIA) is the most common pediatric rheumatic disease; however, little is known about its wider health impacts. This study explores health outcomes associated with JIA genetic liability.

Methods

We used publicly available genetic data sets to interrogate the genetic correlation between JIA and 832 other health-related traits using linkage disequilibrium score regression. Two-sample Mendelian randomization (2SMR) was used to examine four genetic correlates for evidence of causality.

Results

We found robust evidence (adjusted P [Padj] < 0.05) of genetic correlation between JIA and rheumatoid arthritis (genetic correlation [rg] = 0.63, Padj = 0.029), hypothyroidism/myxedema (rg = 0.61, Padj = 0.041), celiac disease (CD) (rg = 0.58, Padj = 0.032), systemic lupus erythematosus (rg = 0.40, Padj = 0.032), coronary artery disease (CAD) (rg = 0.42, Padj = 0.006), number of noncancer illnesses (rg = 0.42, Padj = 0.016), paternal health (rg = 0.57, Padj = 0.032), and strenuous sports (rg = −0.52, Padj = 0.032). 2SMR analyses found robust evidence that genetic liability to JIA was causally associated with the number of noncancer illnesses reported by UK Biobank (UKBB) participants (increase of 0.03 noncancer illnesses per doubling odds of JIA, 95% confidence interval 0.01-0.05).

Conclusion

This study illustrates genetic sharing between JIA and a diversity of health outcomes. The causal association between genetic liability to JIA and noncancer illnesses suggests a need for broader health assessments of patients with JIA to reduce their potential comorbid burden. The strength of genetic correlation with hypothyroidism and CD implies that patients with JIA may benefit from CD and thyroid function screening. Strong positive genetic correlation between JIA and CAD supports the need for cardiovascular risk assessment and risk factor modification.

Original languageEnglish
Pages (from-to)363-370
Number of pages8
JournalACR Open Rheumatology
Volume4
Issue number4
Early online date25 Jan 2022
DOIs
Publication statusE-pub ahead of print - 25 Jan 2022

Bibliographical note

Funding Information:
Dr. Clarke's work was supported by the Wellcome Trust (grant 211030/Z/18/Z as part of grant 203918/Z/16/Z). For the purpose of Open Access, the author has applied a CC BY public copyright license to any author-accepted manuscript version arising from this submission. Prof. Relton's work was supported by the Medical Research Council and the University of Bristol (MC_UU_00011/5). The funders had no input in the study design.

Publisher Copyright:
© 2022 The Authors. ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.

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