BackgroundObservational studies have indicated that peripheral blood eosinophil count is elevated in individuals diagnosed with ulcerative colitis (UC) and correlates with the disease activity of UC. However, this conclusion contradicts with findings from other studies. Therefore, we employed Mendelian randomization (MR) method to assess the genetic link between eosinophil count and UC.MethodThis MR study utilized summary data from genome‐wide association studies (GWAS) on eosinophil count and UC. The main approach used for conducting MR analysis was the inverse variance weighted (IVW) method. Meta‐analysis of the IVW results was performed alongside multiple sensitivity analyses to confirm the robustness of the MR analysis results.ResultsThe IVW method unveiled a causal relationship between eosinophil count and UC (OR = 1.18, 95% CI: 1.04–1.33, p = .01) in the discovery cohort. This finding was further corroborated by the replication cohorts (OR = 1.16, 95% CI: 1.04–1.29, p = .01; OR = 1.12, 95% CI: 1.01–1.24, p = .03). The meta‐analysis indicated that the overall odds ratio (OR) for all studies was 1.15 (common effect model, 95% CI: 1.08–1.23, p < .01). Sensitivity analysis suggested the absence of heterogeneity and horizontal pleiotropy in all MR analyses.ConclusionBased on bidirectional two‐sample MR analysis, there is an indication that elevated eosinophil count may increase the risk of UC. However, potential confounding factors cannot be ruled out, and further research is necessary to explore how eosinophils contribute to the onset and progression of UC.

中文翻译：

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欧洲人群中的嗜酸性粒细胞和溃疡性结肠炎的风险：来自孟德尔随机研究的证据

背景观察性研究表明，诊断患有溃疡性结肠炎（UC）的个体外周血嗜酸性粒细胞计数升高，并且与 UC 的疾病活动性相关。然而，这一结论与其他研究的结果相矛盾。因此，我们采用孟德尔随机化 (MR) 方法来评估嗜酸性粒细胞计数与 UC 之间的遗传联系。方法本 MR 研究利用了关于嗜酸性粒细胞计数和 UC 的全基因组关联研究 (GWAS) 的汇总数据。进行MR分析的主要方法是逆方差加权（IVW）方法。 IVW 结果的荟萃分析与多重敏感性分析一起进行，以确认 MR 分析结果的稳健性。结果 IVW 方法揭示了嗜酸性粒细胞计数与 UC 之间的因果关系（OR = 1.18，95% CI：1.04–1.33，p= .01) 在发现队列中。复制队列进一步证实了这一发现（OR = 1.16，95% CI：1.04–1.29，p= .01； OR = 1.12，95% CI：1.01–1.24，p= .03)。荟萃分析表明，所有研究的总体比值比 (OR) 为 1.15（共同效应模型，95% CI：1.08–1.23，p< .01)。敏感性分析表明所有 MR 分析均不存在异质性和水平多效性。结论基于双向双样本 MR 分析，有迹象表明嗜酸性粒细胞计数升高可能会增加 UC 的风险。然而，不能排除潜在的混杂因素，需要进一步研究来探索嗜酸性粒细胞如何促进 UC 的发生和进展。