TY - JOUR T1 - Association of novel rare coding variants with juvenile idiopathic arthritis JF - Annals of the Rheumatic Diseases JO - Ann Rheum Dis DO - 10.1136/annrheumdis-2020-218359 SP - annrheumdis-2020-218359 AU - Xinyi Meng AU - Xiaoyuan Hou AU - Ping Wang AU - Joseph T Glessner AU - Hui-Qi Qu AU - Michael E March AU - Sipeng Zhang AU - Xiaohui Qi AU - Chonggui Zhu AU - Kenny Nguyen AU - Xinyi Gao AU - Xiaoge Li AU - Yichuan Liu AU - Wentao Zhou AU - Shuyue Zhang AU - Junyi Li AU - Yan Sun AU - Jie Yang AU - Patrick M A Sleiman AU - Qianghua Xia AU - Hakon Hakonarson AU - Jin Li Y1 - 2021/01/05 UR - http://ard.bmj.com/content/early/2021/01/05/annrheumdis-2020-218359.abstract N2 - Objective Juvenile idiopathic arthritis (JIA) is the most common type of arthritis among children, but a few studies have investigated the contribution of rare variants to JIA. In this study, we aimed to identify rare coding variants associated with JIA for the genome-wide landscape.Methods We established a rare variant calling and filtering pipeline and performed rare coding variant and gene-based association analyses on three RNA-seq datasets composed of 228 JIA patients in the Gene Expression Omnibus against different sets of controls, and further conducted replication in our whole-exome sequencing (WES) data of 56 JIA patients. Then we conducted differential gene expression analysis and assessed the impact of recurrent functional coding variants on gene expression and signalling pathway.Results By the RNA-seq data, we identified variants in two genes reported in literature as JIA causal variants, as well as additional 63 recurrent rare coding variants seen only in JIA patients. Among the 44 recurrent rare variants found in polyarticular patients, 10 were replicated by our WES of patients with the same JIA subtype. Several genes with recurrent functional rare coding variants have also common variants associated with autoimmune diseases. We observed immune pathways enriched for the genes with rare coding variants and differentially expressed genes.Conclusion This study elucidated a novel landscape of recurrent rare coding variants in JIA patients and uncovered significant associations with JIA at the gene pathway level. The convergence of common variants and rare variants for autoimmune diseases is also highlighted in this study. ER -