Integrative Genetics Analysis of Juvenile Idiopathic Arthritis Identifies Novel Loci

Li, Yun R.; Li, Jin; Glessner, Joseph; Yang, Jie; March, Michael; Kao, Charlly; Bradfield, Jonathan P.; Li, Junyi; Mentch, Frank; Qu, Hui‐Qi; Qi, Xiaohui; Chang, Xiao; Hou, Cuiping; Abrams, Debra; Qiu, Haijun; Wei, Zhi; Connolly, John J.; Snyder, James W.; Limou, Sophie; Flatø, Berit; Førr, Øystein; Thompson, Susan D.; Langefeld, Carl D.; Glass, David N.; Becker, Mara L.; Perez, Elena E.; Lie, Benedicte A.; Punaro, Marilynn; Shivers, Debra K.; Ellis, Justine A.; Munro, Jane; Wise, Carol A.; Sleiman, Patrick; Hákonarson, Hákon

doi:10.1101/2020.09.01.20185603

Cited by 2 publications

(1 citation statement)

References 69 publications

(96 reference statements)

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“…Many HLA alleles, including HLA class I and class II genes, and common variants in non-HLA genetic loci have been identified in several works, including genome-wide association studies in different JIA subtypes [7][8][9][10][11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

Genome Sequencing in an Individual Presenting with 22q11.2 Deletion Syndrome and Juvenile Idiopathic Arthritis

de Oliveira-Sobrinho,

Appenzeller,

Holanda

et al. 2024

Genes

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Juvenile idiopathic arthritis is a heterogeneous group of diseases characterized by arthritis with poorly known causes, including monogenic disorders and multifactorial etiology. 22q11.2 proximal deletion syndrome is a multisystemic disease with over 180 manifestations already described. In this report, the authors describe a patient presenting with a short stature, neurodevelopmental delay, and dysmorphisms, who had an episode of polyarticular arthritis at the age of three years and eight months, resulting in severe joint limitations, and was later diagnosed with 22q11.2 deletion syndrome. Investigation through Whole Genome Sequencing revealed that he had no pathogenic or likely-pathogenic variants in both alleles of the MIF gene or in genes associated with monogenic arthritis (LACC1, LPIN2, MAFB, NFIL3, NOD2, PRG4, PRF1, STX11, TNFAIP3, TRHR, UNC13DI). However, the patient presented 41 risk polymorphisms for juvenile idiopathic arthritis. Thus, in the present case, arthritis seems coincidental to 22q11.2 deletion syndrome, probably caused by a multifactorial etiology. The association of the MIF gene in individuals previously described with juvenile idiopathic arthritis and 22q11.2 deletion seems unlikely since it is located in the distal and less-frequently deleted region of 22q11.2 deletion syndrome.

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Section: Introductionmentioning

confidence: 99%

Genome Sequencing in an Individual Presenting with 22q11.2 Deletion Syndrome and Juvenile Idiopathic Arthritis

de Oliveira-Sobrinho,

Appenzeller,

Holanda

et al. 2024

Genes

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Association of novel rare coding variants with juvenile idiopathic arthritis

et al. 2021

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ObjectiveJuvenile 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.MethodsWe 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.ResultsBy 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.ConclusionThis 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.

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Integrative Genetics Analysis of Juvenile Idiopathic Arthritis Identifies Novel Loci

Cited by 2 publications

References 69 publications

Genome Sequencing in an Individual Presenting with 22q11.2 Deletion Syndrome and Juvenile Idiopathic Arthritis

Genome Sequencing in an Individual Presenting with 22q11.2 Deletion Syndrome and Juvenile Idiopathic Arthritis

Association of novel rare coding variants with juvenile idiopathic arthritis

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