@misc{10481/77727,
year = {2022},
month = {1},
url = {https://hdl.handle.net/10481/77727},
abstract = {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 (P¼<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.},
organization = {Versus Arthritis	20542	
22084	
20621},
organization = {Centre for Epidemiology Versus Arthritis (UK)	21755},
organization = {National Institute for Health Research (NIHR)},
organization = {Manchester Academic Health Sciences Centre (MAHSC)},
organization = {CLUSTER consortium},
organization = {UK Research & Innovation (UKRI)},
organization = {Medical Research Council UK (MRC)	MR/R013926/1},
organization = {Great Ormond Street Hospital Children's Charity	VS0518},
organization = {Olivia's Vision},
organization = {NIHR GOSH BRC},
organization = {'UK's Experimental Arthritis Treatment Centre for Children by Versus Arthritis	20621},
organization = {NIHR GOSH Biomedical Research Centre},
organization = {British Society for Rheumatology (BSR)},
publisher = {Oxford University Press},
keywords = {JIA},
keywords = {Genetics},
keywords = {Disease outcome},
title = {No evidence that genetic predictors of susceptibility predict changes in core outcomes in JIA},
doi = {10.1093/rheumatology/keab942},
author = {Yarwood, Annie and López Isac, Elena and Childhood Arthritis Prospective Study (CAPS) Group},
}