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

2010; Nature Portfolio; Volume: 42; Issue: 2 Linguagem: Inglês

10.1038/ng.513

1546-1718

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

Psoriasis: Treatment and Pathogenesis

Matthew Brown, John Reveille and colleagues report a genome-wide association study for ankylosing spondylitis. They identify four genetic loci outside of the MHC newly associated to AS susceptibility. 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.