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The causal association between Celiac disease and Ankylosing spondylitis: a two-sample Mendelian randomization

Meiqi Chen¹, Xiang Gao²

¹Department of Basic Medical Sciences, Qinghai University Medical College, Xining, Qinghai, 810016, China. 1948407@qq.com.

BMC Rheumatology

|October 20, 2026

Abstract

Objective:

The concept of the gut-joint axis is often mentioned when exploring the pathogenesis of Ankylosing spondylitis (AS). This study aims to explore whether there is a causal association between Celiac disease (CeD) and AS.

Method:

Two-sample Mendelian randomization (MR) analysis was conducted using the CeD dataset (the largest pure CeD phenotype dataset in the IEU OpenGWAS database at the time of data retrieval, n = 24,269) and the AS dataset (strictly defined, from the IEU OpenGWAS database, n = 218,030). Inverse Variance Weighting (IVW) was adopted as the primary MR analysis method, supplemented by Weighted Median Estimator, MR-Egger regression, Simple Mode, and Weighted Mode to comprehensively evaluate the causal association between CeD and AS. Additionally, horizontal pleiotropy, heterogeneity, and leave-one-out analysis were performed to further evaluate the robustness and reliability of the results.

Results:

IVW analysis showed a positive causal effect of genetically predicted CeD on AS (OR: 1.435, 95% CI: 1.210-1.702, p = 3.34E-05), and the other four analytical methods also yielded consistent causal effect evaluation results. No significant horizontal pleiotropy or heterogeneity was observed in this study.

Conclusion:

MR analysis indicates that CeD may be a potential risk factor for AS, providing genetic evidence for the increased risk of AS in individuals with a genetic predisposition to CeD.

Keywords:

Ankylosing spondylitis Celiac disease Mendelian randomization autoimmune diseases gut-joint axis seronegative arthritis

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Genome-wide Association Studies-GWAS

Genome-wide Association Studies-GWAS

Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
GWAS does not require the identification of the target gene involved in...

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