■嗜酸细胞性食管炎(EoE)和炎症性肠病(IBD),包括克罗恩病(CD)和溃疡性结肠炎(UC),是免疫介导的胃肠道疾病,具有重叠的发病机制,有时同时诊断,但其因果关系尚不清楚。我们通过双样本双向孟德尔随机化(MR)方法研究了EoE和IBD及其亚型之间的因果关系。
■使用全基因组关联研究(GWAS)对欧洲血统个体的汇总数据进行MR分析。独立的单核苷酸多态性与EoE(来自包含1,930例和13,634例对照的GWAS荟萃分析)和IBD(来自包含9,083例IBD的FinnGenGWAS,2,033CD,和5,931个UC病例,和含有12,882个IBD的IBD遗传联盟的GWAS,6,968UC,和5,956例CD病例)被选中作为工具。我们应用逆方差加权(IVW)方法作为主要分析,然后进行一些敏感性分析。对于前向MR研究,随后使用随机效应模型对IVW方法的估计值进行荟萃分析。
■我们的结果表明EoE对IBD有因果关系[合并优势比(OR),1.07;95%置信区间(CI),1.02-1.13]和UC上的EoE(合并OR,1.09,95%CI,1.04-1.14)。未观察到EoE和CD之间的因果关系(合并OR,1.05;95%CI,0.96-1.16)。反向MR分析显示IBD(及其亚型)对EoE没有因果关系。敏感性分析证实了主要结果的稳健性。
■我们的发现提供了EoE对欧洲人群IBD(特别是UC)的暗示因果效应的证据。需要提高EoE患者对并发或后续IBD的认识。尽管如此,目前的证据还不够充分,应该通过进一步的调查加以证实。
UNASSIGNED: Eosinophilic esophagitis (EoE) and inflammatory bowel diseases (IBDs), including Crohn\'s disease (CD) and ulcerative colitis (UC), are immune-mediated gastrointestinal diseases with overlapped pathogenesis and are sometimes concurrently diagnosed, but their causal relationship remains unclear. We investigated the causal relationship between EoE and IBD and its subtypes via a two-sample bidirectional Mendelian randomization (MR) approach.
UNASSIGNED: MR analyses were performed using summary data of a genome-wide association
study (GWAS) on individuals of European ancestry. Independent single-nucleotide polymorphisms correlated with EoE (from a GWAS meta-analysis containing 1,930 cases and 13,634 controls) and IBD (from FinnGen GWASs containing 9,083 IBD, 2,033 CD, and 5,931 UC cases, and GWASs of IBD genetic consortium containing 12,882 IBD, 6,968 UC, and 5,956 CD cases) were selected as instruments. We applied the inverse variance weighted (IVW) method as the primary analysis followed by several sensitivity analyses. For the forward MR
study, estimates from IVW methods were subsequently meta-analyzed using a random-effect model.
UNASSIGNED: Our results suggested a causal effect of EoE on IBD [pooled odds ratio (OR), 1.07; 95% confidence interval (CI), 1.02-1.13] and EoE on UC (pooled OR, 1.09, 95% CI, 1.04-1.14). No causal link between EoE and CD was observed (pooled OR, 1.05; 95% CI, 0.96-1.16). The reverse MR analyses revealed no causal effect of IBD (and its subtypes) on EoE. Sensitivity analyses confirmed the robustness of primary results.
UNASSIGNED: Our findings provided evidence of a suggestive causal effect of EoE on IBD (specifically on UC) in the European population. Increased awareness of concurrent or subsequent IBD in patients with EoE is called for. Still, the present evidence is not adequate enough and ought to be validated by further investigations.