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The genetic associations of acute anterior uveitis and their overlap with the genetics of ankylosing spondylitis

The genetic associations of acute anterior uveitis and their overlap with the genetics of ankylosing spondylitis
The genetic associations of acute anterior uveitis and their overlap with the genetics of ankylosing spondylitis
Acute anterior uveitis (AAU) involves inflammation of the iris and ciliary body of the eye. It occurs both in isolation and as a complication of ankylosing spondylitis (AS). It is strongly associated with HLA-B*27, but previous studies have suggested that further genetic factors may confer additional risk. We sought to investigate this using the Illumina Exomechip microarray, to compare 1504 cases with AS and AAU, 1805 with AS but no AAU and 21?133 healthy controls. We also used a heterogeneity test to test the differences in effect size between AS with AAU and AS without AAU. In the analysis comparing AS+AAU+ cases versus controls, HLA-B*27 and HLA-A*02:01 were significantly associated with the presence of AAU (P<10(-300) and P=6 × 10(-8), respectively). Secondary independent association with PSORS1C3 (P=4.7 × 10(-5)) and TAP2 (P=1.1 × 10(-5)) were observed in the major histocompatibility complex. There was a new suggestive association with a low-frequency variant at zinc-finger protein 154 in the AS without AAU versus control analysis (zinc-finger protein 154 (ZNF154), P=2.2 × 10(-6)). Heterogeneity testing showed that rs30187 in ERAP1 has a larger effect on AAU compared with that in AS alone. These findings also suggest that variants in ERAP1 have a differential impact on the risk of AAU when compared with AS, and hence the genetic risk for AAU differs from AS.
1466-4879
46-51
Robinson, P.C.
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Leo, P.J.
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Pointon, J.J.
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Harris, J.
702c54d7-f4cb-41af-b5e9-63a51c8533b8
Cremin, K.
f9ed10b8-a865-44a8-8e03-338a77346a81
Bradbury, L.A.
be8e0c48-d62d-4cd9-8805-fdd9e33c4244
Stebbings, S.
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Evans, D.M.
3f4a34eb-cd9a-408f-a889-4292f16ad988
Harrison, A.A.
769deaaf-16fd-48c6-ace9-ee4b38a761c1
Duncan, E.L.
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Wordsworth, B.P.
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Brown, M.A.
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Dennison, Elaine
ee647287-edb4-4392-8361-e59fd505b1d1
Robinson, P.C.
59efdb46-58b0-42c8-89f3-0eda34a33dda
Leo, P.J.
5dbf6328-835a-4f91-8990-69aa861ec012
Pointon, J.J.
355413ee-2d58-4e40-a7a2-9b3d23ba4b56
Harris, J.
702c54d7-f4cb-41af-b5e9-63a51c8533b8
Cremin, K.
f9ed10b8-a865-44a8-8e03-338a77346a81
Bradbury, L.A.
be8e0c48-d62d-4cd9-8805-fdd9e33c4244
Stebbings, S.
1d79a80d-6d98-4ad9-bb23-7ec582d235d1
Evans, D.M.
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Harrison, A.A.
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Duncan, E.L.
8075dd7a-c55c-4f9a-9cd6-258a73b366c1
Wordsworth, B.P.
329141d3-5544-4b67-a09c-a5bc4a528169
Brown, M.A.
36371d36-f9d5-4cc8-84ab-18804072fdc7
Dennison, Elaine
ee647287-edb4-4392-8361-e59fd505b1d1

Robinson, P.C., Leo, P.J. and Pointon, J.J. et al. (2016) The genetic associations of acute anterior uveitis and their overlap with the genetics of ankylosing spondylitis. Genes and Immunity, 17 (1), 46-51. (doi:10.1038/gene.2015.49). (PMID:26610302)

Record type: Article

Abstract

Acute anterior uveitis (AAU) involves inflammation of the iris and ciliary body of the eye. It occurs both in isolation and as a complication of ankylosing spondylitis (AS). It is strongly associated with HLA-B*27, but previous studies have suggested that further genetic factors may confer additional risk. We sought to investigate this using the Illumina Exomechip microarray, to compare 1504 cases with AS and AAU, 1805 with AS but no AAU and 21?133 healthy controls. We also used a heterogeneity test to test the differences in effect size between AS with AAU and AS without AAU. In the analysis comparing AS+AAU+ cases versus controls, HLA-B*27 and HLA-A*02:01 were significantly associated with the presence of AAU (P<10(-300) and P=6 × 10(-8), respectively). Secondary independent association with PSORS1C3 (P=4.7 × 10(-5)) and TAP2 (P=1.1 × 10(-5)) were observed in the major histocompatibility complex. There was a new suggestive association with a low-frequency variant at zinc-finger protein 154 in the AS without AAU versus control analysis (zinc-finger protein 154 (ZNF154), P=2.2 × 10(-6)). Heterogeneity testing showed that rs30187 in ERAP1 has a larger effect on AAU compared with that in AS alone. These findings also suggest that variants in ERAP1 have a differential impact on the risk of AAU when compared with AS, and hence the genetic risk for AAU differs from AS.

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Accepted/In Press date: 15 October 2015
e-pub ahead of print date: 26 November 2015
Published date: January 2016
Organisations: Faculty of Medicine

Identifiers

Local EPrints ID: 388702
URI: http://eprints.soton.ac.uk/id/eprint/388702
ISSN: 1466-4879
PURE UUID: 6351f0bf-bf59-48cb-a90c-8bb62ecf3eeb
ORCID for Elaine Dennison: ORCID iD orcid.org/0000-0002-3048-4961

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Date deposited: 02 Mar 2016 11:27
Last modified: 18 Feb 2021 16:46

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Contributors

Author: P.C. Robinson
Author: P.J. Leo
Author: J.J. Pointon
Author: J. Harris
Author: K. Cremin
Author: L.A. Bradbury
Author: S. Stebbings
Author: D.M. Evans
Author: A.A. Harrison
Author: E.L. Duncan
Author: B.P. Wordsworth
Author: M.A. Brown
Author: Elaine Dennison ORCID iD

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