Genome-wide association study of anterior uveitis.

Background/aims: The purpose of this study is to define genetic factors associated with anterior uveitis through genome-wide association study (GWAS).

Methods: 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 (PheWAS) to investigate associations across phenotypes and traits. We also evaluated genetic correlations of anterior uveitis.

Results: We identified six anterior uveitis-associated loci. Genome-wide significant (p<5 × 10) associations were identified for the first time at three loci (innate immunity activator (, nucleotide-binding domain, leucine-rich repeat family, pyrin domain containing 3 and nitric oxide synthase 2). We detected associations at three loci previously reported to be associated with uveitis (endoplasmic reticulum aminopeptidase 1 (, the trinucleotide repeat containing 18 ( and the region) and also replicated associations at two loci previously associated with acute anterior uveitis ( and ). In PheWAS, we further detected that lead single nucleotide polymorphisms (SNPs) at three of the anterior uveitis-associated loci (, and ) 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 ( =0.39, p=8 × 10).

Conclusion: 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.