| Title: | A large meta-analysis identifies genes associated with anterior uveitis |
| Journal: | Nature Communications |
| Published: | 11 Nov 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/37949852/ |
| DOI: | https://doi.org/10.1038/s41467-023-43036-1 |
| URL: | https://www.nature.com/articles/s41467-023-43036-1.pdf |
Publication 8351
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Abstract
Anterior Uveitis (AU) is the inflammation of the anterior part of the eye, the iris and ciliary body and is strongly associated with HLA-B*27. We report AU exome sequencing results from eight independent cohorts consisting of 3,850 cases and 916,549 controls. We identify common genome-wide significant loci in HLA-B (OR = 3.37, p = 1.03e-196) and ERAP1 (OR = 0.86, p = 1.1e-08), and find IPMK (OR = 9.4, p = 4.42e-09) and IDO2 (OR = 3.61, p = 6.16e-08) as genome-wide significant genes based on the burden of rare coding variants. Dividing the cohort into HLA-B*27 positive and negative individuals, we find ERAP1 haplotype is strongly protective only for B*27-positive AU (OR = 0.73, p = 5.2e-10). Investigation of B*27-negative AU identifies a common signal near HLA-DPB1 (rs3117230, OR = 1.26, p = 2.7e-08), risk genes IPMK and IDO2, and several additional candidate risk genes, including ADGFR5, STXBP2, and ACHE. Taken together, we decipher the genetics underlying B*27-positive and -negative AU and identify rare and common genetic signals for both subtypes of disease.</p>
22 Authors
- Sahar Gelfman
- Arden Moscati
- Santiago Mendez Huergo
- Rujin Wang
- Veera Rajagopal
- Neelroop Parikshak
- Vijay Kumar Pounraja
- Esteban Chen
- Michelle Leblanc
- Ralph Hazlewood
- Jan Freudenberg
- Blerta Cooper
- Ann J. Ligocki
- Charles G. Miller
- Tavé Van Zyl
- Jonathan Weyne
- Carmelo Romano
- Botir Sagdullaev
- Olle Melander
- Aris Baras
- Eli A. Stahl
- Giovanni Coppola
1 Application
| Application ID | Title |
|---|---|
| 26041 | Large-Scale Sequencing in the UK Biobank to Facilitate Gene Discovery, Genome Sciences, and Precision Medicine |
Enabling scientific discoveries that improve human health