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

P C Robinson; P J Leo; J J Pointon; K Cremin; L A Bradbury; Peter Donnelly (chair); Ines Barroso (deputy Chair); Jenefer M Blackwell; Elvira Bramon; Matthew A Brown; Juan P Casas; Aiden Corvin; Panos Deloukas; Audrey Duncanson; Janusz Jankowski; Hugh S Markus; Christopher G Mathew; Colin Na Palmer; Robert Plomin; Anna Rautanen; Stephen J Sawcer; Richard C Trembath; Ananth C Viswanathan; Nicholas W Wood; Chris Ca Spencer; Gavin Band; Céline Bellenguez; Colin Freeman; Garrett Hellenthal; Eleni Giannoulatou; Matti Pirinen; Richard Pearson; Amy Strange; Zhan Su; Damjan Vukcevic; Peter Donnelly; Cordelia Langford; Sarah E Hunt; Sarah Edkins; Rhian Gwilliam; Hannah Blackburn; Suzannah J Bumpstead; Serge Dronov; Matthew Gillman; Emma Gray; Naomi Hammond; Alagurevathi Jayakumar; Owen T Mccann; Jennifer Liddle; Simon C Potter; Radhi Ravindrarajah; Michelle Ricketts; Matthew Waller; Paul Weston; Sara Widaa; Pamela Whittaker; Ines Barroso; Panos Deloukas; Christopher G Mathew (chair); Jenefer M Blackwell; Matthew A Brown; Aiden Corvin; Chris C A Spencer; Eugene Mccloskey; John Eisman; Graeme Jones; Geoff Nicholson; Richard Eastell; Philip Sambrook; Richard Prince; Elaine Dennison; Ian Reid; John Wark; S Stebbings; A A Harrison; D M Evans; E L Duncan; B P Wordsworth; M A Brown

doi:10.1038/gene.2015.49

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

P C Robinson, P J Leo, J J Pointon, K Cremin, L A Bradbury, Peter Donnelly (chair), Ines Barroso (deputy Chair), Jenefer M Blackwell, Elvira Bramon, Matthew A Brown, Juan P Casas, Aiden Corvin, Panos Deloukas, Audrey Duncanson, Janusz Jankowski, Hugh S Markus, Christopher G Mathew, Colin Na Palmer, Robert Plomin, Anna RautanenStephen J Sawcer, Richard C Trembath, Ananth C Viswanathan, Nicholas W Wood, Chris Ca Spencer, Gavin Band, Céline Bellenguez, Colin Freeman, Garrett Hellenthal, Eleni Giannoulatou, Matti Pirinen, Richard Pearson, Amy Strange, Zhan Su, Damjan Vukcevic, Peter Donnelly, Cordelia Langford, Sarah E Hunt, Sarah Edkins, Rhian Gwilliam, Hannah Blackburn, Suzannah J Bumpstead, Serge Dronov, Matthew Gillman, Emma Gray, Naomi Hammond, Alagurevathi Jayakumar, Owen T Mccann, Jennifer Liddle, Simon C Potter, Radhi Ravindrarajah, Michelle Ricketts, Matthew Waller, Paul Weston, Sara Widaa, Pamela Whittaker, Ines Barroso, Panos Deloukas, Christopher G Mathew (chair), Jenefer M Blackwell, Matthew A Brown, Aiden Corvin, Chris C A Spencer, Eugene Mccloskey, John Eisman, Graeme Jones, Geoff Nicholson, Richard Eastell, Philip Sambrook, Richard Prince, Elaine Dennison, Ian Reid, John Wark, S Stebbings, A A Harrison, D M Evans, E L Duncan, B P Wordsworth, M A Brown

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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.

Original language	English
Pages (from-to)	46-51
Journal	GENES AND IMMUNITY
Volume	17
Issue number	1
Early online date	26 Nov 2015
DOIs	https://doi.org/10.1038/gene.2015.49
Publication status	E-pub ahead of print - 26 Nov 2015

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10.1038/gene.2015.49

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Robinson, P. C., Leo, P. J., Pointon, J. J., Cremin, K., Bradbury, L. A., Donnelly (chair), P., Barroso (deputy Chair), I., M Blackwell, J., Bramon, E., Brown, M. A., Casas, J. P., Corvin, A., Deloukas, P., Duncanson, A., Jankowski, J., Markus, H. S., Mathew, C. G., Palmer, C. N., Plomin, R., ... Brown, M. A. (2015). The genetic associations of acute anterior uveitis and their overlap with the genetics of ankylosing spondylitis. GENES AND IMMUNITY, 17(1), 46-51. Advance online publication. https://doi.org/10.1038/gene.2015.49

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title = "The genetic associations of acute anterior uveitis and their overlap with the genetics of ankylosing spondylitis",

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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Robinson, PC, Leo, PJ, Pointon, JJ, Cremin, K, Bradbury, LA, Donnelly (chair), P, Barroso (deputy Chair), I, M Blackwell, J, Bramon, E, Brown, MA, Casas, JP, Corvin, A, Deloukas, P, Duncanson, A, Jankowski, J, Markus, HS, Mathew, CG, Palmer, CN, Plomin, R, Rautanen, A, Sawcer, SJ, Trembath, RC , Viswanathan, AC, Wood, NW, Spencer, CC, Band, G, Bellenguez, C, Freeman, C, Hellenthal, G, Giannoulatou, E, Pirinen, M, Pearson, R, Strange, A, Su, Z, Vukcevic, D, Donnelly, P, Langford, C, Hunt, SE, Edkins, S, Gwilliam, R, Blackburn, H, Bumpstead, SJ, Dronov, S, Gillman, M, Gray, E, Hammond, N, Jayakumar, A, Mccann, OT, Liddle, J, Potter, SC, Ravindrarajah, R, Ricketts, M, Waller, M, Weston, P, Widaa, S, Whittaker, P, Barroso, I, Deloukas, P, Mathew (chair), CG, Blackwell, JM, Brown, MA, Corvin, A, Spencer, CCA, Mccloskey, E, Eisman, J, Jones, G, Nicholson, G, Eastell, R, Sambrook, P, Prince, R, Dennison, E, Reid, I, Wark, J, Stebbings, S, Harrison, AA, Evans, DM, Duncan, EL, Wordsworth, BP & Brown, MA 2015, 'The genetic associations of acute anterior uveitis and their overlap with the genetics of ankylosing spondylitis', GENES AND IMMUNITY, vol. 17, no. 1, pp. 46-51. https://doi.org/10.1038/gene.2015.49

TY - JOUR

T1 - The genetic associations of acute anterior uveitis and their overlap with the genetics of ankylosing spondylitis

AU - Robinson, P C

AU - Leo, P J

AU - Pointon, J J

AU - Cremin, K

AU - Bradbury, L A

AU - Donnelly (chair), Peter

AU - Barroso (deputy Chair), Ines

AU - M Blackwell, Jenefer

AU - Bramon, Elvira

AU - Brown, Matthew A

AU - Casas, Juan P

AU - Corvin, Aiden

AU - Deloukas, Panos

AU - Duncanson, Audrey

AU - Jankowski, Janusz

AU - Markus, Hugh S

AU - Mathew, Christopher G

AU - Palmer, Colin Na

AU - Plomin, Robert

AU - Rautanen, Anna

AU - Sawcer, Stephen J

AU - Trembath, Richard C

AU - Viswanathan, Ananth C

AU - Wood, Nicholas W

AU - Spencer, Chris Ca

AU - Band, Gavin

AU - Bellenguez, Céline

AU - Freeman, Colin

AU - Hellenthal, Garrett

AU - Giannoulatou, Eleni

AU - Pirinen, Matti

AU - Pearson, Richard

AU - Strange, Amy

AU - Su, Zhan

AU - Vukcevic, Damjan

AU - Donnelly, Peter

AU - Langford, Cordelia

AU - Hunt, Sarah E

AU - Edkins, Sarah

AU - Gwilliam, Rhian

AU - Blackburn, Hannah

AU - Bumpstead, Suzannah J

AU - Dronov, Serge

AU - Gillman, Matthew

AU - Gray, Emma

AU - Hammond, Naomi

AU - Jayakumar, Alagurevathi

AU - Mccann, Owen T

AU - Liddle, Jennifer

AU - Potter, Simon C

AU - Ravindrarajah, Radhi

AU - Ricketts, Michelle

AU - Waller, Matthew

AU - Weston, Paul

AU - Widaa, Sara

AU - Whittaker, Pamela

AU - Barroso, Ines

AU - Deloukas, Panos

AU - Mathew (chair), Christopher G

AU - Blackwell, Jenefer M

AU - Brown, Matthew A

AU - Corvin, Aiden

AU - Spencer, Chris C A

AU - Mccloskey, Eugene

AU - Eisman, John

AU - Jones, Graeme

AU - Nicholson, Geoff

AU - Eastell, Richard

AU - Sambrook, Philip

AU - Prince, Richard

AU - Dennison, Elaine

AU - Reid, Ian

AU - Wark, John

AU - Stebbings, S

AU - Harrison, A A

AU - Evans, D M

AU - Duncan, E L

AU - Wordsworth, B P

AU - Brown, M A

PY - 2015/11/26

Y1 - 2015/11/26

N2 - 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.

AB - 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.

U2 - 10.1038/gene.2015.49

DO - 10.1038/gene.2015.49

M3 - Article

SN - 1466-4879

VL - 17

SP - 46

EP - 51

JO - GENES AND IMMUNITY

JF - GENES AND IMMUNITY

IS - 1

ER -

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

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