The British journal of ophthalmology · 2025
Genome-wide association study of anterior uveitis.
СтатьяМетаанализНазвание и аннотация: Перевод в очереди
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Koskimäki Fredrika, Ahokas Oona, Kajanne Risto, Saviauk Krista-Roberta, Elnahas Abdelrahman, Reigo Anu, Reis Kadri, Esko Tõnu, Palta Priit, Leinonen Sanna, Kettunen Johannes, Liinamaa Johanna, Karjalainen Minna K, Saarela Ville, Estonian Biobank Research Team Consortium, FinnGen Consortium, FinnGen Consortium
Аннотация
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 × 10-8) associations were identified for the first time at three loci (innate immunity activator (INAVA), 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 (ERAP1), the trinucleotide repeat containing 18 (TNRC18) and the HLA region) and also replicated associations at two loci previously associated with acute anterior uveitis (IL23R and HDAC2-AS2). In PheWAS, we further detected that lead single nucleotide polymorphisms (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 (rg =0.39, p=8 × 10-5).
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.
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 × 10-8) associations were identified for the first time at three loci (innate immunity activator (INAVA), 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 (ERAP1), the trinucleotide repeat containing 18 (TNRC18) and the HLA region) and also replicated associations at two loci previously associated with acute anterior uveitis (IL23R and HDAC2-AS2). In PheWAS, we further detected that lead single nucleotide polymorphisms (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 (rg =0.39, p=8 × 10-5).
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.