A large meta-analysis identifies genes associated with anterior uveitis
Gelfman, S. ; Melander, O. LU
and Coppola, G.
(2023)
In Nature Communications
14(1).
- 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... (More)
- 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. © 2023, The Author(s). (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/9916066b-6cc3-4a0b-87fc-7331e54d72eb
- author
- Gelfman, S.
; Melander, O.
LU
and Coppola, G.
- author collaboration
- organization
- publishing date
- 2023
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Aminopeptidases, Genes, MHC Class I, Genetic Predisposition to Disease, Haplotypes, HLA-B Antigens, Humans, Inflammation, Minor Histocompatibility Antigens, Polymorphism, Single Nucleotide, Uveitis, Anterior, acetylcholinesterase, HLA B antigen, HLA DPB1 antigen, aminopeptidase, ERAP1 protein, human, minor histocompatibility antigen, cohort analysis, genetics, genome, meta-analysis, signal, allele, Article, controlled study, enzyme activity, gene frequency, gene locus, genetic association, genetic risk, genetic variability, genotype, genotyping, haplotype, human, iridocyclitis, meta analysis, population, skeletal muscle, whole exome sequencing, gene, genetic predisposition, inflammation, single nucleotide polymorphism
- in
- Nature Communications
- volume
- 14
- issue
- 1
- article number
- 7300
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:85176222319
- pmid:37949852
- ISSN
- 2041-1723
- DOI
- 10.1038/s41467-023-43036-1
- language
- English
- LU publication?
- yes
- id
- 9916066b-6cc3-4a0b-87fc-7331e54d72eb
- date added to LUP
- 2024-01-16 14:44:39
- date last changed
- 2025-06-26 16:56:24
@article{9916066b-6cc3-4a0b-87fc-7331e54d72eb,
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. © 2023, The Author(s).}},
author = {{Gelfman, S. and Melander, O. and Coppola, G.}},
issn = {{2041-1723}},
keywords = {{Aminopeptidases; Genes, MHC Class I; Genetic Predisposition to Disease; Haplotypes; HLA-B Antigens; Humans; Inflammation; Minor Histocompatibility Antigens; Polymorphism, Single Nucleotide; Uveitis, Anterior; acetylcholinesterase; HLA B antigen; HLA DPB1 antigen; aminopeptidase; ERAP1 protein, human; minor histocompatibility antigen; cohort analysis; genetics; genome; meta-analysis; signal; allele; Article; controlled study; enzyme activity; gene frequency; gene locus; genetic association; genetic risk; genetic variability; genotype; genotyping; haplotype; human; iridocyclitis; meta analysis; population; skeletal muscle; whole exome sequencing; gene; genetic predisposition; inflammation; single nucleotide polymorphism}},
language = {{eng}},
number = {{1}},
publisher = {{Nature Publishing Group}},
series = {{Nature Communications}},
title = {{A large meta-analysis identifies genes associated with anterior uveitis}},
url = {{http://dx.doi.org/10.1038/s41467-023-43036-1}},
doi = {{10.1038/s41467-023-43036-1}},
volume = {{14}},
year = {{2023}},
}