Session Type: ACR Concurrent Abstract Session
Session Time: 2:30PM-4:00PM
Background/Purpose: Behçet’s disease is a chronic relapsing inflammatory disease characterized by recurrent mucocutaneous involvement. We performed dense genotyping in immune related loci in a large multi-ethnic cohort of Behçet’s disease patients and controls to further characterize the genetic basis of this disease.
Methods: We studied 5 independent cohorts of Behçet’s disease patients and controls consisting of 1253 patients and 5799 controls from Turkey, Italy, Spain, Japan, and Korea. Genotyping was performed using the Immunochip platform (Illumina), which includes ~200,000 genetic variants in immune-related genetic loci. Genetic association analysis in each cohort and a meta-analysis were performed to identify genetic susceptibility loci for Behçet’s disease. Additional genetic variants were imputed up to the 1000 Genomes Project density. Conditional genetic analysis and functional mapping using epigenetic marks of enhancer regions and expression quantitative trait loci (eQTL) analyses were performed to further characterize the genetic effects identified.
Results: We identified and fine-mapped genetic associations for Behçet’s disease with a GWAS level of significance in a lncRNA near QSOX2 (OR= 1.82, P= 1.08E-8), RASIP1/FUT2 (OR= 1.41, P= 3.57E-09), and IL12A-AS1 (OR= 1.71, P= 4.19E-08). The genetic association within the RASIP1/FUT2 locus is located within an active enhancer region as indicated by H3K27 acetylation marks. The disease risk variant in this locus is associated with mRNA expression changes of multiple transcripts within this locus, including significantly increased expression of RASIP1 and decreased expression of FUT2 in mucocutaneous tissues, frequently a target in Behçet’s disease. The association in the QSOX2 genetic locus can be localized to genetic variants within WI2-1959D15.1, which is a 1235bp lncRNA, and is associated with increased expression of this transcript. Several previously identified susceptibility loci for Behçet’s disease were also replicated.
Conclusion: We performed dense genotyping in immune-related genes in a multi-ethnic cohort of Behçet’s disease patients and controls, and identified a novel genetic susceptibility locus in a lncRNA near QSOX2, a genetic association with a functional genetic variant within an enhancer region in RASIP1/FUT2, and replicated the recently reported association in IL12A-AS1.
To cite this abstract in AMA style:Renauer P, Coit P, Hughes T, Ognenovski M, Adler A, Ortiz-Fernández L, Yilmaz V, Aksu K, Duzgun N, Keser G, Cefle A, Yazici A, Ergen A, Alpsoy E, Salvarani C, Casali B, Koetter I, Zhernakova A, Wijmenga C, Takeuchi F, Harihara S, Kaburaki T, Song YW, Carmona FD, Alarcon Riquelme ME, Martín J, Saruhan-Direskeneli G, Gonzalez Escribano MF, Direskeneli H, Sawalha AH. Dense Genotyping of Immune Related Loci in a Multi-Ethnic Behçet’s Disease Cohort Identifies Genetic Associations in a Long Noncoding RNA Near QSOX2, RASIP1/FUT2, and IL12A-AS1 [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/dense-genotyping-of-immune-related-loci-in-a-multi-ethnic-behcets-disease-cohort-identifies-genetic-associations-in-a-long-noncoding-rna-near-qsox2-rasip1fut2-and-il12a-as1/. Accessed September 29, 2023.
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