Objective

The aim of this study was to investigate the potential causal relationship between ankylosing spondylitis (AS) and ovarian cancer.

Methods

We conducted analyses utilizing publicly available pooled statistical data sets from genomewide association studies (GWAS) involving individuals of European ancestry. Our objective was to identify single nucleotide polymorphisms (SNPs) significantly associated with AS and use them as instrumental variables to assess the causal relationship between AS and ovarian cancer. We employed three statistical methods for two-sample Mendelian randomization: inverse variance weighting (IVW), weighted median, and MR‐Egger regression. Network MR Analysis revealed the mediating role of tumor necrosis factor receptor superfamily member 21 between ankylosing spondylitis and ovarian cancer.

Results

From the GWAS on AS, we selected 23 instrumental SNPs that exhibited genome-wide significance. Our findings consistently demonstrated an association between AS and ovarian cancer using multiple statistical methods (IVW: odds ratio (OR) 1.147, 95% confidence interval (CI) 1.022–1.287; weighted median estimator: OR 1.177, 95% CI 1.009–1.373; MR-Egger regression: OR 1.166, 95% CI 0.958–1.418). These results indicate a positive correlation, suggesting that AS is associated with an increased risk of ovarian cancer. Furthermore, there was no evidence to suggest that the observed causal effect between AS and the risk of osteoarthritis was influenced by genetic pleiotropy (MR-Egger intercept = -0.0010644, P = 0.8433359). In addition, tumor necrosis factor receptor superfamily member 21 mediated 10.2% of the total effect size in the development of ankylosing spondylitis on ovarian cancer risk.

Conclusion

Our Mendelian randomization analysis provides strong evidence supporting a potential causal relationship between AS and ovarian cancer risk, with ankylosing spondylitis clearly associated with an increased risk of ovarian cancer. Tumor necrosis factor receptor superfamily member 21 as a mediator involved in the occurrence and development of these two diseases.

中文翻译：

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强直性脊柱炎与卵巢癌风险之间的因果关系

客观的

本研究的目的是调查强直性脊柱炎（AS）与卵巢癌之间的潜在因果关系。

方法

我们利用来自涉及欧洲血统个体的全基因组关联研究 (GWAS) 的公开汇总统计数据集进行了分析。我们的目标是确定与 AS 显着相关的单核苷酸多态性 (SNP)，并将其用作工具变量来评估 AS 与卵巢癌之间的因果关系。我们采用三种统计方法进行双样本孟德尔随机化：逆方差加权 (IVW)、加权中位数和 MR-Egger 回归。网络MR分析揭示了肿瘤坏死因子受体超家族成员21在强直性脊柱炎和卵巢癌之间的介导作用。

结果

从 AS 的 GWAS 中，我们选择了 23 个具有全基因组意义的有用 SNP。我们的研究结果使用多种统计方法一致证明了 AS 与卵巢癌之间的关联（IVW：比值比 (OR) 1.147，95% 置信区间 (CI) 1.022–1.287；加权中值估计量：OR 1.177，95% CI 1.009–1.373； MR-Egger 回归：OR 1.166，95% CI 0.958–1.418)。这些结果表明呈正相关，表明 AS 与卵巢癌风险增加相关。此外，没有证据表明所观察到的 AS 与骨关节炎风险之间的因果关系受到遗传多效性的影响（MR-Egger 截距 = -0.0010644，P = 0.8433359）。此外，肿瘤坏死因子受体超家族成员21介导的强直性脊柱炎发展对卵巢癌风险的总影响大小为10.2%。

结论

我们的孟德尔随机化分析提供了强有力的证据，支持 AS 与卵巢癌风险之间的潜在因果关系，其中强直性脊柱炎明显与卵巢癌风险增加相关。肿瘤坏死因子受体超家族成员21作为介质参与了这两种疾病的发生和发展。