Nature Communications (Nov 2023)

A large meta-analysis identifies genes associated with anterior uveitis

  • 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,
  • Regeneron Genetics Center,
  • Eli A. Stahl,
  • Giovanni Coppola

DOI
https://doi.org/10.1038/s41467-023-43036-1
Journal volume & issue
Vol. 14, no. 1
pp. 1 – 13

Abstract

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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.