Association of Variants at 1q32 and <em>STAT3</em> with Ankylosing Spondylitis Suggests Genetic Overlap with Crohn's Disease
Bibliographic record
Abstract
<div><p>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 <em>KIF21B</em> (rs11584383, <em>P</em> = 1.6×10<sup>−10</sup>, odds ratio (OR) = 0.74, 95% CI:0.68–0.82). Association with disease was also detected for 2 variants within <em>STAT3</em> (rs6503695, <em>P</em> = 4.6×10<sup>−4</sup>. OR = 0.86 (95% CI:0.79–0.93); rs744166, <em>P</em> = 2.6×10<sup>−5</sup>, OR = 0.84 (95% CI:0.77–0.91)). Association was confirmed for <em>IL23R</em> (rs11465804, <em>P</em> = 1.2×10<sup>−5</sup>, OR = 0.65 (95% CI:0.54–0.79)), and further associations were detected for <em>IL12B</em> (rs10045431, <em>P</em> = 5.2×10<sup>−5</sup>, OR = 0.83 (95% CI:0.76–0.91)), <em>CDKAL1</em> (rs6908425, <em>P</em> = 1.1×10<sup>−4</sup>, OR = 0.82 (95% CI:0.74–0.91)), <em>LRRK2/MUC19</em> (rs11175593, <em>P</em> = 9.9×10<sup>−5</sup>, OR = 1.92 (95% CI: 1.38–2.67)), and chr13q14 (rs3764147, <em>P</em> = 5.9×10<sup>−4</sup>, 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 <em>STAT3</em> as ankylosing spondylitis susceptibility loci. It also further confirms association for <em>IL23R</em> 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.</p></div>
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.005 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".