Genetic dissection of acute anterior uveitis reveals similarities and differences in associations observed with ankylosing spondylitis

Robinson, Philip C., Claushuis, Theodora A. M., Cortes, Adrian, Martin, Tammy M., Evans, David M., Leo, Paul, Mukhopadhyay, Pamela, Bradbury, Linda A., Cremin, Katie, Harris, Jessica, Maksymowych, Walter P., Inman, Robert D., Rahman, Proton, Haroon, Nigil, Gensler, Lianne, Powell, Joseph E., Van Der Horst-Bruinsma, Irene E., Hewitt, Alex W., Craig, Jamie E., Lim, Lyndell L., Wakefield, Denis, McCluskey, Peter, Voigt, Valentina, Fleming, Peter, Spondyloarthritis Research Consortium of Canada, Australio-Anglo-American Spondylitis Consortium, International Genetics of Ankylosing Spondylitis Consortium, Wellcome Trust Case Control Study 2, Degli-Esposti, Mariapia, Pointon, Jennifer J., Weisman, Michael H., Wordsworth, B. Paul, Reveille, John D., Rosenbaum, James T. and Brown, Matthew A. (2015) Genetic dissection of acute anterior uveitis reveals similarities and differences in associations observed with ankylosing spondylitis. Arthritis and Rheumatology, 67 1: 140-151. doi:10.1002/art.38873

Author Robinson, Philip C.
Claushuis, Theodora A. M.
Cortes, Adrian
Martin, Tammy M.
Evans, David M.
Leo, Paul
Mukhopadhyay, Pamela
Bradbury, Linda A.
Cremin, Katie
Harris, Jessica
Maksymowych, Walter P.
Inman, Robert D.
Rahman, Proton
Haroon, Nigil
Gensler, Lianne
Powell, Joseph E.
Van Der Horst-Bruinsma, Irene E.
Hewitt, Alex W.
Craig, Jamie E.
Lim, Lyndell L.
Wakefield, Denis
McCluskey, Peter
Voigt, Valentina
Fleming, Peter
Spondyloarthritis Research Consortium of Canada
Australio-Anglo-American Spondylitis Consortium
International Genetics of Ankylosing Spondylitis Consortium
Wellcome Trust Case Control Study 2
Degli-Esposti, Mariapia
Pointon, Jennifer J.
Weisman, Michael H.
Wordsworth, B. Paul
Reveille, John D.
Rosenbaum, James T.
Brown, Matthew A.
Title Genetic dissection of acute anterior uveitis reveals similarities and differences in associations observed with ankylosing spondylitis
Journal name Arthritis and Rheumatology   Check publisher's open access policy
ISSN 2326-5205
Publication date 2015-01-01
Year available 2014
Sub-type Article (original research)
DOI 10.1002/art.38873
Open Access Status DOI
Volume 67
Issue 1
Start page 140
End page 151
Total pages 12
Place of publication Hoboken, NJ, United States
Publisher John Wiley and Sons
Language eng
Formatted abstract
To use high-density genotyping to investigate the genetic associations of acute anterior uveitis (AAU) in patients with and those without ankylosing spondylitis (AS).

We genotyped samples from 1,711 patients with AAU (either primary or combined with AS), 2,339 AS patients without AAU, and 10,000 control subjects on an Illumina Immunochip Infinium microarray. We also used data for AS patients from previous genome-wide association studies to investigate the AS risk locus ANTXR2 for its putative effect in AAU. ANTXR2 expression in mouse eyes was investigated by real-time quantitative reverse transcription–polymerase chain reaction.

A comparison between all patients with AAU and healthy control subjects showed strong association over HLA–B, corresponding to the HLA–B27 tag single-nucleotide polymorphism rs116488202. The association of 3 non–major histocompatibility complex loci, IL23R, the intergenic region 2p15, and ERAP1, reached genome-wide significance (P < 5 × 10−8). Five loci harboring the immune-related genes IL10–IL19, IL18R1–IL1R1, IL6R, the chromosome 1q32 locus harboring KIF21B, as well as the eye-related gene EYS, were also associated, reaching a suggestive level of significance (P < 5 × 10−6). Several previously confirmed AS associations demonstrated significant differences in effect size between AS patients with AAU and AS patients without AAU. ANTXR2 expression varied across eye compartments.

These findings of both novel AAU-specific associations and associations shared with AS demonstrate overlapping but also distinct genetic susceptibility loci for AAU and AS. The associations in IL10 and IL18R1 are shared with inflammatory bowel disease, suggesting common etiologic pathways.
Keyword Rheumatology
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID UL1TR000124
Institutional Status UQ
Additional Notes Published online 27 December 2014

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2015 Collection
UQ Diamantina Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 24 times in Thomson Reuters Web of Science Article | Citations
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