SynthesisClinical rheumatology2025
GWAS meta-analysis of axial spondyloarthritis and Behçet's disease identifies CXCR6 as a novel MHC-I-opathy gene in a Turkish population.
Synthesis in Clinical rheumatology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectiveAxial spondyloarthritis (AxSpA) and Behçet's disease (BD) have clinical and HLA locus overlap and have been grouped under MHC-I-opathy. This study aimed to identify overlapping loci between AxSpA and BD to help elucidate MHC-I-opathy pathogenesis.
methodsAssociation clustering methods, such as OASIS, reduce the multiple-testing burden and are more powerful than single variant analysis for identifying modest genetic effects. Two large publicly available genome-wide association studies (GWAS) of AxSpA (921 cases, 907 controls) and BD (1215 cases and 1278 healthy controls) from Turkiÿe were subjected to OASIS meta-analyses to identify common non-HLA loci. Statistics used to identify significant loci included the novel OASIS locus index (OLI). Expression analysis was performed using GEO datasets, GSE181364 for AxSpA and GSE209567 for BD. STRING network analysis was performed.
resultsGWAS for both diseases had the highest significance at the HLA-I locus. Of the 234 independent modestly significant non-HLA loci, there were 15 loci common to both AxSpA and BD. These included known MHC-I-opathy loci, 1p31.3 for IL23R (P = 5.37 × 10
conclusionSeveral loci containing pathologically relevant genes for MHC-I-opathy were identified here, using a cluster-based approach in AxSpA and BD GWAS, with CXCR6 being a novel target. Key Points • MHC-I-opathy immunopathogenesis is incompletely understood and challenged by risk genes of modest effect. • This meta-analysis identified 15 loci common to both AxSpA and BD that may provide diagnostic and therapeutic targets for MHC-I-opathy. • Major candidate genes for MHC-I-opathy identified here are IL23R, LACC1, and CXCR6. • FBXL2 was associated strongly with BD by OASIS analysis.
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