Association of Variants at 1q32 and STAT3 with Ankylosing Spondylitis Suggests Genetic Overlap with Crohn's Disease

2015202 citationsJournal Articlegreen Open Access

Authors

Patrick Danoy · The University of Queensland

Karena Pryce · The University of Queensland

Johanna Hadler · The University of Queensland

Linda A. Bradbury · The University of Queensland

Claire Farrar · Nuffield Orthopaedic Centre

Jennifer J. Pointon · Nuffield Orthopaedic Centre

Michael M. Ward

Abstract

<div>Ankylosing spondylitis (AS) is a common inflammatory arthritic condition. Overt inflammatory bowel disease (IBD) occurs in about 10% of AS patients, and in addition 70% of AS cases may have subclinical terminal ileitis. Spondyloarthritis is also common in IBD patients. We therefore tested Crohn's disease susceptibility genes for association with AS, aiming to identify pleiotropic genetic associations with both diseases. Genotyping was carried out using Sequenom and Applied Biosystems TaqMan and OpenArray technologies on 53 markers selected from 30 Crohn's disease associated genomic regions. We tested genotypes in a population of unrelated individual cases (n = 2,773) and controls (n = 2,215) of white European ancestry for association with AS. Statistical analysis was carried out using a Cochran-Armitage test for trend in PLINK. Strong association was detected at chr1q32 near KIF21B (rs11584383, P = 1.6×10−10, odds ratio (OR) = 0.74, 95% CI:0.68–0.82). Association with disease was also detected for 2 variants within STAT3 (rs6503695, P = 4.6×10−4. OR = 0.86 (95% CI:0.79–0.93); rs744166, P = 2.6×10−5, OR = 0.84 (95% CI:0.77–0.91)). Association was confirmed for IL23R (rs11465804, P = 1.2×10−5, OR = 0.65 (95% CI:0.54–0.79)), and further associations were detected for IL12B (rs10045431, P = 5.2×10−5, OR = 0.83 (95% CI:0.76–0.91)), CDKAL1 (rs6908425, P = 1.1×10−4, OR = 0.82 (95% CI:0.74–0.91)), LRRK2/MUC19 (rs11175593, P = 9.9×10−5, OR = 1.92 (95% CI: 1.38–2.67)), and chr13q14 (rs3764147, P = 5.9×10−4, OR = 1.19 (95% CI: 1.08–1.31)). Excluding cases with clinical IBD did not significantly affect these findings. This study identifies chr1q32 and STAT3 as ankylosing spondylitis susceptibility loci. It also further confirms association for IL23R and detects suggestive association with another 4 loci. STAT3 is a key signaling molecule within the Th17 lymphocyte differentiation pathway and further enhances the case for a major role of this T-lymphocyte subset in ankylosing spondylitis. Finally these findings suggest common aetiopathogenic pathways for AS and Crohn's disease and further highlight the involvement of common risk variants across multiple diseases.</div>

Topics & Keywords

Inflammatory Bowel Disease Spondyloarthritis Studies and Treatments Systemic Lupus Erythematosus Research

UN Sustainable Development Goals

Good health and well-being

Publication Details

Published in: Figshare

DOI: 10.1371/journal.pgen.1001195

Command Palette

Association of Variants at 1q32 and &lt;em&gt;STAT3&lt;/em&gt; with Ankylosing Spondylitis Suggests Genetic Overlap with Crohn's Disease

Authors

Abstract

Topics & Keywords

UN Sustainable Development Goals

Publication Details

Association of Variants at 1q32 and <em>STAT3</em> with Ankylosing Spondylitis Suggests Genetic Overlap with Crohn's Disease