{"doi":"10.1002/art.42129","title":"Identification of Novel Loci Shared by Juvenile Idiopathic Arthritis Subtypes Through Integrative Genetic Analysis","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.","journal":"Arthritis & Rheumatology","year":2022,"id":266431,"datarank":0.3720145038505112,"base_score":2.302585092994046,"endowment":2.302585092994046,"self_citation_contribution":0.3453877639491069,"citation_network_contribution":0.026626739901404305,"self_endowment_contribution":0.3453877639491069,"citer_contribution":0.026626739901404305,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":6,"citers_with_citation_signal":2,"citers_with_endowment":2,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9517,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":515141,"name":"Leslie A. 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