Journal article

Genomic risk scores for juvenile idiopathic arthritis and its subtypes

Rodrigo Canovas, Joanna Cobb, Marta Brozynska, John Bowes, Yun R Li, Samantha Louise Smith, Hakon Hakonarson, Wendy Thomson, Justine A Ellis, Gad Abraham, Jane E Munro, Michael Inouye

Annals of the Rheumatic Diseases | BMJ PUBLISHING GROUP | Published : 2020

Abstract

OBJECTIVES: Juvenile idiopathic arthritis (JIA) is an autoimmune disease and a common cause of chronic disability in children. Diagnosis of JIA is based purely on clinical symptoms, which can be variable, leading to diagnosis and treatment delays. Despite JIA having substantial heritability, the construction of genomic risk scores (GRSs) to aid or expedite diagnosis has not been assessed. Here, we generate GRSs for JIA and its subtypes and evaluate their performance. METHODS: We examined three case/control cohorts (UK, US-based and Australia) with genome-wide single nucleotide polymorphism (SNP) genotypes. We trained GRSs for JIA and its subtypes using lasso-penalised linear models in cross-..

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Grants

Awarded by Australian National Health and Medical Research Council (NHMRC)


Awarded by Royal Children's Hospital Foundation


Awarded by UK Medical Research Council


Awarded by British Heart Foundation


Awarded by NHMRC


Awarded by Arthritis Research UK


Awarded by Versus Arthritis


Awarded by Sparks UK


Awarded by Medical Research Council


Awarded by NIH


Funding Acknowledgements

This study was supported in part by the Victorian Government's OIS Program, the Australian National Health and Medical Research Council (NHMRC Project no. 1122744), the Murdoch Children's Research Institute and the Royal Children's Hospital Foundation (grant no. 2017-896). This work was supported by core funding from the UK Medical Research Council (MR/L003120/1), the British Heart Foundation (RG/13/13/30194; RG/18/13/33946) and the National Institute for Health Research (Cambridge Biomedical Research Centre at the Cambridge University Hospitals NHS Foundation Trust)*. It was also supported by Health Data Research UK, which is funded by the UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, Department of Health and Social Care (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation and Wellcome. GA was supported by an NHMRC Early Career Fellowship (no. 1090462). MI was supported by the Munz Chair of Cardiovascular Prediction and Prevention. This study acknowledges the use of the following UK JIA cohort collections: The Biologics for Children with Rheumatic Diseases (BCRD) study (funded by Arthritis Research UK Grant 20747). The British Society for Paediatric and Adolescent Rheumatology Etanercept Cohort Study (BSPAR--ETN) (funded by a research grant from the British Society for Rheumatology (BSR). BSR has previously also received restricted income from Pfizer to fund this project). Childhood Arthritis Prospective Study (CAPS) (funded by Versus Arthritis, grant reference number 20542), Childhood Arthritis Response to Medication Study (CHARMS) (funded by Sparks UK, reference 08ICH09, and the Medical Research Council, reference MR/M004600/1), United Kingdom Juvenile Idiopathic Arthritis Genetics Consortium (UKJIAGC). Genotyping of the UK JIA case samples were supported by the Versus Arthritis grants reference numbers 20 385 and 21 754. This research was funded by the NIHR Manchester Biomedical Research Centre and supported by the Manchester Academic Health Sciences Centre (MAHSC). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. We would like to acknowledge the assistance given by IT Services and the use of the Computational Shared Facility at The University of Manchester. Finally, the CHOP data used were funded by an Institute Development Fund to the CAG centre from The Children's Hospital of Philadelphia and by NIH grant, U01-HG006830, from the NHGRI-sponsored eMERGE Network.