Dataset Information

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

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 [P_adj ] < 0.05) of genetic correlation between JIA and rheumatoid arthritis (genetic correlation [r_g ] = 0.63, P_adj = 0.029), hypothyroidism/myxedema (r_g = 0.61, P_adj = 0.041), celiac disease (CD) (r_g = 0.58, P_adj = 0.032), systemic lupus erythematosus (r_g = 0.40, P_adj = 0.032), coronary artery disease (CAD) (r_g = 0.42, P_adj = 0.006), number of noncancer illnesses (r_g = 0.42, P_adj = 0.016), paternal health (r_g = 0.57, P_adj = 0.032), and strenuous sports (r_g = -0.52, P_adj = 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.

SUBMITTER: Clarke SLN

PROVIDER: S-EPMC8992462 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Publications

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

Clarke Sarah L N SLN Richmond Rebecca C RC Zheng Jie J Spiller Wes W Ramanan Athimalaipet V AV Sharp Gemma C GC Relton Caroline L CL

ACR open rheumatology 20220125 4

<h4>Objective</h4>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.<h4>Methods</h4>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 genet ...[more]

PMID: 35077020

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Project description:ImportancePatients with juvenile idiopathic arthritis (JIA) may develop adult rheumatic diseases later in life, and prolonged or recurrent disease activity is often associated with substantial disability; therefore, it is important to identify patients with JIA at high risk of developing adult rheumatic diseases and provide specialized attention and preventive care to them.ObjectiveTo elucidate the full extent of the genetic association of JIA with adult rheumatic diseases, to improve treatment strategies and patient outcomes for patients at high risk of developing long-term rheumatic diseases.Design, setting, and participantsIn this genetic association study of 4 disease genome-wide association study (GWAS) cohorts from 2013 to 2024 (JIA, rheumatoid arthritis [RA], systemic lupus erythematosus [SLE], and systemic sclerosis [SSc]), patients in the JIA cohort were recruited from the US, Australia, and Norway (with a UK cohort included in the meta-analyzed cohort), while patients in the other 3 cohorts were recruited from US and Western European countries. All analyses were conducted between September 2023 and April 2024.ExposuresGenetic associations.Main outcomes and measuresGenetic correlations and shared genomic loci between JIA and adult rheumatic diseases. Genetic correlation analyses and cross-trait meta-analysis were conducted on the JIA cohort and the summary statistics of the GWASs from adult rheumatic diseases (RA, SLE, and SSc). Mendelian randomization analyses were also conducted.ResultsThis study included 33 207 patients across the 4 cohorts, with 4550 patients in the meta-analyzed JIA cohort (JIA cohort: 1485 patients with arthritis onset before 16 years; 1017 female [68.5%]; 10 352 controls; UK cohort: 3305 patients with JIA; 9196 controls), 143 61 patients in the RA cohort, 5201 patients in the SLE cohort; and 9095 patients in the SSc cohort. After the GWAS result of the JIA cohort was meta-analyzed with the UK JIA cohort, there was a total of 4550 JIA cases and 18 446 controls. The analysis revealed a significant global correlation between JIA and adult rheumatic diseases, with 84 regions harboring signals associated with multiple diseases. Cross-trait analyses uncovered novel disease loci and 20 loci associated with JIA and adult diseases. Mendelian randomization analysis revealed the significant association of 11 proteins with rheumatic disorders. Both shared, organ-specific, and disease-specific critical cell types were highlighted.Conclusions and relevanceIn this genetic association study, there was significant genetic overlap between JIA and adult rheumatic diseases. These findings may help to refine JIA classification, risk stratification, and therapeutic strategy of repurposing adult disease drugs for pediatric patients with similar mechanisms.

Dataset Information

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

Objective

Methods

Results

Conclusion

Publications

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

Similar Datasets

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