"Identification of Novel Loci Shared by Juvenile Idiopathic Arthritis S" by Jin Li, Yun R. Li et al.
 

Identification of Novel Loci Shared by Juvenile Idiopathic Arthritis Subtypes Through Integrative Genetic Analysis

Document Type

Article

Publication Date

8-1-2022

Abstract

Objective: Juvenile idiopathic arthritis (JIA) is the most common chronic immune-mediated joint disease among children and encompasses a heterogeneous group of immune-mediated joint disorders classified into 7 subtypes according to clinical presentation. However, phenotype overlap and biologic evidence suggest a shared mechanistic basis between subtypes. This study was undertaken to systematically investigate shared genetic underpinnings of JIA subtypes. Methods: We performed a heterogeneity-sensitive genome-wide association study encompassing a total of 1,245 JIA cases (classified into 7 subtypes) and 9,250 controls, followed by fine-mapping of candidate causal variants at each genome-wide significant locus, functional annotation, and pathway and network analysis. We further identified candidate drug targets and drug repurposing opportunities by in silico analyses. Results: In addition to the major histocompatibility complex locus, we identified 15 genome-wide significant loci shared between at least 2 JIA subtypes, including 10 novel loci. Functional annotation indicated that candidate genes at these loci were expressed in diverse immune cell types. Conclusion: This study identified novel genetic loci shared by JIA subtypes. Our findings identified candidate mechanisms underlying JIA subtypes and candidate targets with drug repurposing opportunities for JIA treatment.

Identifier

85134025799 (Scopus)

Publication Title

Arthritis and Rheumatology

External Full Text Location

https://doi.org/10.1002/art.42129

e-ISSN

23265205

ISSN

23265191

PubMed ID

35347896

First Page

1420

Last Page

1429

Issue

8

Volume

74

Grant

F32

Fund Ref

National Institutes of Health

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