Browse by author
Lookup NU author(s): Emerita Professor Helen Foster, Dr Flora McErlane
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0).
© 2022 The Author(s). Published by Oxford University Press on behalf of the British Society for Rheumatology.Objectives: The clinical progression of JIA is unpredictable. Knowing who will develop severe disease could facilitate rapid intensification of therapies. We use genetic variants conferring susceptibility to JIA to predict disease outcome measures. Methods: A total of 713 JIA patients with genotype data and core outcome variables (COVs) at diagnosis (baseline) and 1 year follow-up were identified from the Childhood Arthritis Prospective Study (CAPS). A weighted genetic risk score (GRS) was generated, including all single nucleotide polymorphisms (SNPs) previously associated with JIA susceptibility (P-value < 5×10-08). We used multivariable linear regression to test the GRS for association with COVS (limited joint count, active joint count, physician global assessment, parent/patient general evaluation, childhood HAQ and ESR) at baseline and change in COVS from baseline to 1 year, adjusting for baseline COV and International League of Associations of Rheumatology (ILAR) category. The GRS was split into quintiles to identify high (quintile 5) and low (quintile 1) risk groups. Results: Patients in the high-risk group for the GRS had a younger age at presentation (median low risk 7.79, median high risk 3.51). No association was observed between the GRS and any outcome measures at 1 year follow-up or baseline. Conclusion: For the first time we have used all known JIA genetic susceptibility loci (P=<5×10-08) in a GRS to predict changes in disease outcome measured over time. Genetic susceptibility variants are poor predictors of changes in core outcome measures, it is likely that genetic factors predicting disease outcome are independent to those predicting susceptibility. The next step will be to conduct a genome-wide association analysis of JIA outcome.
Author(s): Yarwood A, Shoop-Worrall S, Lopez-Isac E, Smith SL, Morris AP, Baildam E, Chieng A, Cleary G, Ciurtin C, Davidson JE, Foster HE, Ioannou Y, McErlane F, Wedderburn LR, Hyrich K, Thomson W, Bowes JD, Tordoff M, Hyrich KL, Thomson W, Eyre S
Publication type: Article
Publication status: Published
Journal: Rheumatology
Year: 2022
Volume: 61
Issue: 10
Pages: 4136-4144
Print publication date: 01/10/2022
Online publication date: 07/01/2022
Acceptance date: 15/12/2021
Date deposited: 09/06/2023
ISSN (print): 1462-0324
ISSN (electronic): 1462-0332
Publisher: Oxford University Press
URL: https://doi.org/10.1093/rheumatology/keab942
DOI: 10.1093/rheumatology/keab942
PubMed id: 35015833
Altmetrics provided by Altmetric
