Genome-wide association study of anterior uveitis

ABSTRACT Importance Anterior uveitis is an intraocular disease characterized by inflammation of the iris and the ciliary body and known to co-occur with autoimmune diseases. This is the largest genome-wide association study (GWAS) meta-analysis specifically for anterior uveitis to date. Objective The purpose of this study is to define genetic factors associated with anterior uveitis through genome-wide association study. Design, setting and participants In this GWAS meta-analysis we combined data from the FinnGen, Estonian Biobank and UK Biobank with a total of 12 205 anterior uveitis cases and 917 145 controls. We performed a phenome-wide association study to investigate associations across phenotypes and traits. We also evaluated genetic correlations of anterior uveitis. Main outcomes and measures Genetic variants associated with anterior uveitis. Results We identified six anterior uveitis associated loci. Genome-wide significant ( p < 5 × 10 −8 ) associations were identified for the first time at three loci ( INAVA, NLRP3 and NOS2 ). We detected associations at three loci previously reported to be associated with uveitis ( ERAP1, TNRC18 and the HLA region) and also replicated associations at two loci previously associated with acute anterior uveitis ( IL23R and HDAC2-AS2 ). In phenome-wide association study, we further detected that lead single nucleotide polymorphism, SNPs, at three of the anterior uveitis associated loci ( ERAP1, INAVA and TNRC18 ) are associated with other immunity-related phenotypes, including ankylosing spondylitis and inflammatory bowel disease. Additionally, we detected a moderate genetic correlation between anterior uveitis and inflammatory bowel disease ( r g =0.39, p = 8 × 10 −5 ). Conclusions and relevance We identified six anterior uveitis associated loci including three novel loci with genome-wide significance. Our findings deepen our understanding of the genetic basis of anterior uveitis and the genetic connections between anterior uveitis and immune related disorders, providing a foundation for further research and potential therapeutic interventions.