Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci

Adrian Cortes; Johanna Hadler; Jenny P. Pointon; Philip C. Robinson; Tugce Karaderi; Paul Leo; Katie Cremin; Karena Pryce; Jessica Harris; Seunghun Lee; Kyung Bin Joo; Seung Cheol Shim; Michael Weisman; Michael Ward; Xiaodong Zhou; Henri Jean Garchon; Gilles Chiocchia; Johannes Nossent; Benedicte A. Lie; Øystein Førre; Jaakko Tuomilehto; Kari Laiho; Lei Jiang; Yu Liu; Xin Wu; Linda A. Bradbury; Dirk Elewaut; Ruben Burgos-Vargas; Simon Stebbings; Louise Appleton; Claire Farrah; Jonathan Lau; Tony J. Kenna; Nigil Haroon; Manuel A. Ferreira; Jian Yang; Juan Mulero; Jose Luis Fernandez-Sueiro; Miguel A. Gonzalez-Gay; Carlos Lopez-Larrea; Panos Deloukas; Peter Donnelly; Paul Bowness; Karl Gafney; Hill Gaston; Dafna D. Gladman; Proton Rahman; Walter P. Maksymowych; Huji Xu; J. Bart A. Crusius

doi:10.1038/ng.2667

Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci

Adrian Cortes, Johanna Hadler, Jenny P. Pointon, Philip C. Robinson, Tugce Karaderi, Paul Leo, Katie Cremin, Karena Pryce, Jessica Harris, Seunghun Lee, Kyung Bin Joo, Seung Cheol Shim, Michael Weisman, Michael Ward, Xiaodong Zhou, Henri Jean Garchon, Gilles Chiocchia, Johannes Nossent, Benedicte A. Lie, Øystein FørreJaakko Tuomilehto, Kari Laiho, Lei Jiang, Yu Liu, Xin Wu, Linda A. Bradbury, Dirk Elewaut, Ruben Burgos-Vargas, Simon Stebbings, Louise Appleton, Claire Farrah, Jonathan Lau, Tony J. Kenna, Nigil Haroon, Manuel A. Ferreira, Jian Yang, Juan Mulero, Jose Luis Fernandez-Sueiro, Miguel A. Gonzalez-Gay, Carlos Lopez-Larrea, Panos Deloukas, Peter Donnelly, Paul Bowness, Karl Gafney, Hill Gaston, Dafna D. Gladman, Proton Rahman, Walter P. Maksymowych, Huji Xu, J. Bart A. Crusius

466 Citations (Scopus)

Abstract

Ankylosing spondylitis is a common, highly heritable inflammatory arthritis affecting primarily the spine and pelvis. In addition to HLA-B*27 alleles, 12 loci have previously been identified that are associated with ankylosing spondylitis in populations of European ancestry, and 2 associated loci have been identified in Asians. In this study, we used the Illumina Immunochip microarray to perform a case-control association study involving 10,619 individuals with ankylosing spondylitis (cases) and 15,145 controls. We identified 13 new risk loci and 12 additional ankylosing spondylitis-associated haplotypes at 11 loci. Two ankylosing spondylitis-associated regions have now been identified encoding four aminopeptidases that are involved in peptide processing before major histocompatibility complex (MHC) class I presentation. Protective variants at two of these loci are associated both with reduced aminopeptidase function and with MHC class I cell surface expression.

Original language	English
Journal	Nature Genetics
Volume	45
Issue number	7
Pages (from-to)	730-738
Number of pages	9
ISSN	1061-4036
DOIs	https://doi.org/10.1038/ng.2667
Publication status	Published - 1 Jul 2013
Externally published	Yes

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Cortes, A., Hadler, J., Pointon, J. P., Robinson, P. C., Karaderi, T., Leo, P., Cremin, K., Pryce, K., Harris, J., Lee, S., Joo, K. B., Shim, S. C., Weisman, M., Ward, M., Zhou, X., Garchon, H. J., Chiocchia, G., Nossent, J., Lie, B. A., ... Crusius, J. B. A. (2013). Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci. Nature Genetics, 45(7), 730-738. https://doi.org/10.1038/ng.2667

Cortes, A, Hadler, J, Pointon, JP, Robinson, PC, Karaderi, T, Leo, P, Cremin, K, Pryce, K, Harris, J, Lee, S, Joo, KB, Shim, SC, Weisman, M, Ward, M, Zhou, X, Garchon, HJ, Chiocchia, G, Nossent, J, Lie, BA, Førre, Ø, Tuomilehto, J, Laiho, K, Jiang, L, Liu, Y, Wu, X, Bradbury, LA, Elewaut, D, Burgos-Vargas, R, Stebbings, S, Appleton, L, Farrah, C, Lau, J, Kenna, TJ, Haroon, N, Ferreira, MA, Yang, J, Mulero, J, Fernandez-Sueiro, JL, Gonzalez-Gay, MA, Lopez-Larrea, C, Deloukas, P, Donnelly, P, Bowness, P, Gafney, K, Gaston, H, Gladman, DD, Rahman, P, Maksymowych, WP, Xu, H & Crusius, JBA 2013, 'Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci', Nature Genetics, vol. 45, no. 7, pp. 730-738. https://doi.org/10.1038/ng.2667

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title = "Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci",

abstract = "Ankylosing spondylitis is a common, highly heritable inflammatory arthritis affecting primarily the spine and pelvis. In addition to HLA-B*27 alleles, 12 loci have previously been identified that are associated with ankylosing spondylitis in populations of European ancestry, and 2 associated loci have been identified in Asians. In this study, we used the Illumina Immunochip microarray to perform a case-control association study involving 10,619 individuals with ankylosing spondylitis (cases) and 15,145 controls. We identified 13 new risk loci and 12 additional ankylosing spondylitis-associated haplotypes at 11 loci. Two ankylosing spondylitis-associated regions have now been identified encoding four aminopeptidases that are involved in peptide processing before major histocompatibility complex (MHC) class I presentation. Protective variants at two of these loci are associated both with reduced aminopeptidase function and with MHC class I cell surface expression.",

author = "Adrian Cortes and Johanna Hadler and Pointon, {Jenny P.} and Robinson, {Philip C.} and Tugce Karaderi and Paul Leo and Katie Cremin and Karena Pryce and Jessica Harris and Seunghun Lee and Joo, {Kyung Bin} and Shim, {Seung Cheol} and Michael Weisman and Michael Ward and Xiaodong Zhou and Garchon, {Henri Jean} and Gilles Chiocchia and Johannes Nossent and Lie, {Benedicte A.} and {\O}ystein F{\o}rre and Jaakko Tuomilehto and Kari Laiho and Lei Jiang and Yu Liu and Xin Wu and Bradbury, {Linda A.} and Dirk Elewaut and Ruben Burgos-Vargas and Simon Stebbings and Louise Appleton and Claire Farrah and Jonathan Lau and Kenna, {Tony J.} and Nigil Haroon and Ferreira, {Manuel A.} and Jian Yang and Juan Mulero and Fernandez-Sueiro, {Jose Luis} and Gonzalez-Gay, {Miguel A.} and Carlos Lopez-Larrea and Panos Deloukas and Peter Donnelly and Paul Bowness and Karl Gafney and Hill Gaston and Gladman, {Dafna D.} and Proton Rahman and Maksymowych, {Walter P.} and Huji Xu and Crusius, {J. Bart A.}",

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AU - Hadler, Johanna

AU - Pointon, Jenny P.

AU - Robinson, Philip C.

AU - Karaderi, Tugce

AU - Leo, Paul

AU - Cremin, Katie

AU - Pryce, Karena

AU - Harris, Jessica

AU - Lee, Seunghun

AU - Joo, Kyung Bin

AU - Shim, Seung Cheol

AU - Weisman, Michael

AU - Ward, Michael

AU - Zhou, Xiaodong

AU - Garchon, Henri Jean

AU - Chiocchia, Gilles

AU - Nossent, Johannes

AU - Lie, Benedicte A.

AU - Førre, Øystein

AU - Tuomilehto, Jaakko

AU - Laiho, Kari

AU - Jiang, Lei

AU - Liu, Yu

AU - Wu, Xin

AU - Bradbury, Linda A.

AU - Elewaut, Dirk

AU - Burgos-Vargas, Ruben

AU - Stebbings, Simon

AU - Appleton, Louise

AU - Farrah, Claire

AU - Lau, Jonathan

AU - Kenna, Tony J.

AU - Haroon, Nigil

AU - Ferreira, Manuel A.

AU - Yang, Jian

AU - Mulero, Juan

AU - Fernandez-Sueiro, Jose Luis

AU - Gonzalez-Gay, Miguel A.

AU - Lopez-Larrea, Carlos

AU - Deloukas, Panos

AU - Donnelly, Peter

AU - Bowness, Paul

AU - Gafney, Karl

AU - Gaston, Hill

AU - Gladman, Dafna D.

AU - Rahman, Proton

AU - Maksymowych, Walter P.

AU - Xu, Huji

AU - Crusius, J. Bart A.

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AB - Ankylosing spondylitis is a common, highly heritable inflammatory arthritis affecting primarily the spine and pelvis. In addition to HLA-B*27 alleles, 12 loci have previously been identified that are associated with ankylosing spondylitis in populations of European ancestry, and 2 associated loci have been identified in Asians. In this study, we used the Illumina Immunochip microarray to perform a case-control association study involving 10,619 individuals with ankylosing spondylitis (cases) and 15,145 controls. We identified 13 new risk loci and 12 additional ankylosing spondylitis-associated haplotypes at 11 loci. Two ankylosing spondylitis-associated regions have now been identified encoding four aminopeptidases that are involved in peptide processing before major histocompatibility complex (MHC) class I presentation. Protective variants at two of these loci are associated both with reduced aminopeptidase function and with MHC class I cell surface expression.

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Identification of multiple risk variants for ankylosing spondylitis through high-density genotyping of immune-related loci

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