Publication: Clinical trait-specific genetic analysis in Behçet's disease identifies novel loci associated with ocular and neurological involvement
Loading...
Files
Date
2023-06-02
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
Behçet’s disease is a complex inflammatory vasculitis with a broad spectrum of clinical
manifestations. The purpose of this study was to investigate the genetics underlying specific
clinical features of Behçet’s disease in a group of patients with > 20 years of follow up. A total of
436 patients with Behçet’s disease from Turkey were studied. Genotyping was performed using
the Infinium ImmunoArray-24 BeadChip. After imputation and quality control measures, logistic
regressions adjusting for sex and the first five principal components were performed for each
clinical trait using a case-case genetic analysis approach. A weighted genetic risk score was
calculated for each clinical feature. Genetic association analyses of previously identified
susceptibility loci in Behçet’s disease revealed a genetic association between ocular lesions and
HLA-B/MICA (rs116799036: OR=1.85, 95% CI=1.35-2.52, p-value=1.1x10-4
). The genetic risk
score was significantly higher in Behçet’s disease patients with ocular lesions compared with those
without ocular involvement, and is explained by the genetic variation in the HLA region. New
genetic loci predisposing to specific clinical features in Behçet’s disease were suggested when
genome-wide variants were evaluated. The most significant associations were observed in ocular
involvement with SLCO4A (rs6062789: OR=0.41 (95% CI=0.30-0.58), p-value=1.92x10-7
), and
neurological involvement with DDX60L (rs62334264: OR= 4.12 (95% CI 2.34 to 7.24), p-value =
8.85x10-7
). Our results emphasize the role of genetic factors in predisposing to specific clinical
manifestations in Behçet’s disease, and might shed additional light into disease heterogeneity,
pathogenesis, and variability of Behçet’s disease presentation across populations.
Description
Keywords
Behçet’s disease, clinical manifestations, genetics, HLA, ocular lesions
Citation
Casares-Marfil D., Esencan D., Alibaz-Oner F., Çefle A., Yazıcı A., Duzgun N., Aşık M. A., Özbek S., Cinar M., Alpsoy E., et al., "Clinical trait-specific genetic analysis in Behçet's disease identifies novel loci associated with ocular and neurological involvement.", Clinical immunology (Orlando, Fla.), ss.109657, 2023