To explore susceptibility loci associated with uveitis in Behcet's disease (BD).
We conducted a genome-wide association study (GWAS) primarily involving 978 BD uveitis cases and 4388 controls and a replication study of 953 BD uveitis cases and 2129 controls in the Chinese population. Luciferase reporter analysis and Chromatin immunoprecipitation (ChIP) assay were performed to explore the functional role of susceptibility genetic variants nearby ZMIZ1.
Three independent HLA alleles (HLA-B51, HLA-A26 and HLA-C0704) were identified in a genome-wide association with BD uveitis. In the non-HLA region, besides confirming 7 previously reported loci, we identified 22 novel susceptibility variants located in 16 loci. Meta-analysis of the Chinese cohort involving 1931 cases and 6517 controls and a published Japanese cohort of 611 cases and 737 controls showed genome-wide significant associations with ZMIZ1, RPS6KA4, IL10RA, SIPA1-FIBP-FOSL1 and VAMP1. Functional experiments demonstrated that genetic variants of ZMIZ1 were associated with an enhanced transcriptional activity and an increased expression of ZMIZ1.
This GWAS study identified a novel set of genetic variants that are associated with susceptibility to uveitis in BD. These findings enriched our understanding of the contribution of genetic factors to the disease.