Genome-wide association study of ankylosing spondylitis identifies non-MHC susceptibility loci

John D Reveille; Anne-Marie Sims; Patrick Danoy; David M Evans; Paul Leo; Jennifer J Pointon; Rui Jin; Xiaodong Zhou; Linda A Bradbury; Louise H Appleton; John C Davis; Laura Diekman; Tracey Doan; Alison Dowling; Ran Duan; Emma L Duncan; Claire Farrar; Johanna Hadler; David Harvey; Tugce Karaderi; Rebecca Mogg; Emma Pomeroy; Karena Pryce; Jacqueline Taylor; Laurie Savage; Panos Deloukas; Vasudev Kumanduri; Leena Peltonen; Sue M Ring; Pamela Whittaker; Evgeny Glazov; Gethin P Thomas; Walter P Maksymowych; Robert D Inman; Michael M Ward; Millicent A Stone; Michael H Weisman; B Paul Wordsworth; Matthew A Brown

doi:10.1038/ng.513

Genome-wide association study of ankylosing spondylitis identifies non-MHC susceptibility loci

John D Reveille, Anne-Marie Sims, Patrick Danoy, David M Evans, Paul Leo, Jennifer J Pointon, Rui Jin, Xiaodong Zhou, Linda A Bradbury, Louise H Appleton, John C Davis, Laura Diekman, Tracey Doan, Alison Dowling, Ran Duan, Emma L Duncan, Claire Farrar, Johanna Hadler, David Harvey, Tugce KaraderiRebecca Mogg, Emma Pomeroy, Karena Pryce, Jacqueline Taylor, Laurie Savage, Panos Deloukas, Vasudev Kumanduri, Leena Peltonen, Sue M Ring, Pamela Whittaker, Evgeny Glazov, Gethin P Thomas, Walter P Maksymowych, Robert D Inman, Michael M Ward, Millicent A Stone, Michael H Weisman, B Paul Wordsworth, Matthew A Brown

Department of Life Sciences

Research output: Contribution to journal › Article › peer-review

562 Citations (SciVal)

Abstract

To identify susceptibility loci for ankylosing spondylitis, we undertook a genome-wide association study in 2,053 unrelated ankylosing spondylitis cases among people of European descent and 5,140 ethnically matched controls, with replication in an independent cohort of 898 ankylosing spondylitis cases and 1,518 controls. Cases were genotyped with Illumina HumHap370 genotyping chips. In addition to strong association with the major histocompatibility complex (MHC; P < 10−800), we found association with SNPs in two gene deserts at 2p15 (rs10865331; combined P = 1.9 × 10−19) and 21q22 (rs2242944; P = 8.3 × 10−20), as well as in the genes ANTXR2 (rs4333130; P = 9.3 × 10−8) and IL1R2 (rs2310173; P = 4.8 × 10−7). We also replicated previously reported associations at IL23R (rs11209026; P = 9.1 × 10−14) and ERAP1 (rs27434; P = 5.3 × 10−12). This study reports four genetic loci associated with ankylosing spondylitis risk and identifies a major role for the interleukin (IL)-23 and IL-1 cytokine pathways in disease susceptibility.

Original language	English
Pages (from-to)	123-127
Number of pages	5
Journal	Nature Genetics
Volume	42
Issue number	2
Early online date	10 Jan 2010
DOIs	https://doi.org/10.1038/ng.513
Publication status	Published - Feb 2010

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Reveille, J. D., Sims, A.-M., Danoy, P., Evans, D. M., Leo, P., Pointon, J. J., Jin, R., Zhou, X., Bradbury, L. A., Appleton, L. H., Davis, J. C., Diekman, L., Doan, T., Dowling, A., Duan, R., Duncan, E. L., Farrar, C., Hadler, J., Harvey, D., ... Brown, M. A. (2010). Genome-wide association study of ankylosing spondylitis identifies non-MHC susceptibility loci. Nature Genetics, 42(2), 123-127. https://doi.org/10.1038/ng.513

Reveille, JD, Sims, A-M, Danoy, P, Evans, DM, Leo, P, Pointon, JJ, Jin, R, Zhou, X, Bradbury, LA, Appleton, LH, Davis, JC, Diekman, L, Doan, T, Dowling, A, Duan, R, Duncan, EL, Farrar, C, Hadler, J, Harvey, D, Karaderi, T, Mogg, R, Pomeroy, E, Pryce, K, Taylor, J, Savage, L, Deloukas, P, Kumanduri, V, Peltonen, L, Ring, SM, Whittaker, P, Glazov, E, Thomas, GP, Maksymowych, WP, Inman, RD, Ward, MM, Stone, MA, Weisman, MH, Wordsworth, BP & Brown, MA 2010, 'Genome-wide association study of ankylosing spondylitis identifies non-MHC susceptibility loci', Nature Genetics, vol. 42, no. 2, pp. 123-127. https://doi.org/10.1038/ng.513

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title = "Genome-wide association study of ankylosing spondylitis identifies non-MHC susceptibility loci",

abstract = "To identify susceptibility loci for ankylosing spondylitis, we undertook a genome-wide association study in 2,053 unrelated ankylosing spondylitis cases among people of European descent and 5,140 ethnically matched controls, with replication in an independent cohort of 898 ankylosing spondylitis cases and 1,518 controls. Cases were genotyped with Illumina HumHap370 genotyping chips. In addition to strong association with the major histocompatibility complex (MHC; P < 10−800), we found association with SNPs in two gene deserts at 2p15 (rs10865331; combined P = 1.9 × 10−19) and 21q22 (rs2242944; P = 8.3 × 10−20), as well as in the genes ANTXR2 (rs4333130; P = 9.3 × 10−8) and IL1R2 (rs2310173; P = 4.8 × 10−7). We also replicated previously reported associations at IL23R (rs11209026; P = 9.1 × 10−14) and ERAP1 (rs27434; P = 5.3 × 10−12). This study reports four genetic loci associated with ankylosing spondylitis risk and identifies a major role for the interleukin (IL)-23 and IL-1 cytokine pathways in disease susceptibility.",

author = "Reveille, {John D} and Anne-Marie Sims and Patrick Danoy and Evans, {David M} and Paul Leo and Pointon, {Jennifer J} and Rui Jin and Xiaodong Zhou and Bradbury, {Linda A} and Appleton, {Louise H} and Davis, {John C} and Laura Diekman and Tracey Doan and Alison Dowling and Ran Duan and Duncan, {Emma L} and Claire Farrar and Johanna Hadler and David Harvey and Tugce Karaderi and Rebecca Mogg and Emma Pomeroy and Karena Pryce and Jacqueline Taylor and Laurie Savage and Panos Deloukas and Vasudev Kumanduri and Leena Peltonen and Ring, {Sue M} and Pamela Whittaker and Evgeny Glazov and Thomas, {Gethin P} and Maksymowych, {Walter P} and Inman, {Robert D} and Ward, {Michael M} and Stone, {Millicent A} and Weisman, {Michael H} and Wordsworth, {B Paul} and Brown, {Matthew A}",

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AU - Reveille, John D

AU - Sims, Anne-Marie

AU - Danoy, Patrick

AU - Evans, David M

AU - Leo, Paul

AU - Pointon, Jennifer J

AU - Jin, Rui

AU - Zhou, Xiaodong

AU - Bradbury, Linda A

AU - Appleton, Louise H

AU - Davis, John C

AU - Diekman, Laura

AU - Doan, Tracey

AU - Dowling, Alison

AU - Duan, Ran

AU - Duncan, Emma L

AU - Farrar, Claire

AU - Hadler, Johanna

AU - Harvey, David

AU - Karaderi, Tugce

AU - Mogg, Rebecca

AU - Pomeroy, Emma

AU - Pryce, Karena

AU - Taylor, Jacqueline

AU - Savage, Laurie

AU - Deloukas, Panos

AU - Kumanduri, Vasudev

AU - Peltonen, Leena

AU - Ring, Sue M

AU - Whittaker, Pamela

AU - Glazov, Evgeny

AU - Thomas, Gethin P

AU - Maksymowych, Walter P

AU - Inman, Robert D

AU - Ward, Michael M

AU - Stone, Millicent A

AU - Weisman, Michael H

AU - Wordsworth, B Paul

AU - Brown, Matthew A

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Genome-wide association study of ankylosing spondylitis identifies non-MHC susceptibility loci

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