Department of Gastroenterology, Ganzhou Municipal Hospital(Guangdong Provincial People's Hospital Ganzhou Hospital), Ganzhou, Jiangxi, China.
Department of Rheumatology and Immunology, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen, Guangdong, China.
Front Immunol. 2023 Dec 14;14:1293511. doi: 10.3389/fimmu.2023.1293511. eCollection 2023.
Numerous observational investigations have documented a correlation between asthma and ulcerative colitis(UC). In this Mendelian Randomization (MR) study, we utilized extensive summary data from Genome-Wide Association Studies (GWAS) to further estimate the association between adult-onset asthma and the risk of UC, and to investigate the role of Interleukin-18 (IL-18) as a potential mediator.
A two-step, two-sample MR study was conducted through mediation analysis. For this study, we employed a two-sample MR analysis using the inverse variance-weighted (IVW), weighted median, weighted mode, and MR-Egger regression techniques. We utilized publicly accessible summary statistics from a GWAS meta-analysis of adult-onset asthma in the UK Biobank (n=327,253; cases=26,582; controls=300,671) as the exposure factor. The outcomes were derived from GWAS data of individuals with European ancestry (n=26,405; cases=6,687; controls=19,718). GWAS data for IL-18 were obtained from individuals of European ancestry (n=9,785,222; cases=3,636; controls=9,781,586).
The MR analysis indicates that adult-onset asthma is associated with an increased risk of UC, with an odds ratio (OR) of 1.019 (95% CI 1.001-1.045, P=0.006). However, there is no strong evidence to suggest that UC significantly impacts the risk of adult-onset asthma. IL-18 may act as a potential mediator in the causal relationship between adult-onset asthma and UC, with a mediation proportion of 3.9% (95% CI, 0.6%-6.9%).
In summary, our study established a causal relationship between asthma and UC, in which IL-18 contributes to a small extent. However, the primary factors underlying the influence of asthma on UC remain unclear. Future research should focus on identifying other potential mediators. In clinical practice, it is important to pay greater attention to intestinal lesions in patients with asthma.
大量观察性研究表明哮喘与溃疡性结肠炎（UC）之间存在相关性。在这项孟德尔随机化（MR）研究中，我们利用全基因组关联研究（GWAS）的广泛汇总数据，进一步估计成人起病哮喘与 UC 风险之间的关联，并探讨白细胞介素-18（IL-18）作为潜在介导物的作用。
通过中介分析进行了两阶段、两样本 MR 研究。在这项研究中，我们使用了两样本 MR 分析，采用了逆方差加权（IVW）、加权中位数、加权众数和 MR-Egger 回归技术。我们使用了英国生物库（UK Biobank）中成人起病哮喘 GWAS 荟萃分析的公开可用汇总统计数据（n=327253；病例=26582；对照=300671）作为暴露因素。结果来自欧洲血统个体的 GWAS 数据（n=26405；病例=6687；对照=19718）。IL-18 的 GWAS 数据来自欧洲血统个体（n=9785222；病例=3636；对照=9781586）。
MR 分析表明，成人起病哮喘与 UC 风险增加相关，比值比（OR）为 1.019（95% CI 1.001-1.045，P=0.006）。然而，没有强有力的证据表明 UC 会显著影响成人起病哮喘的风险。IL-18 可能在成人起病哮喘和 UC 之间的因果关系中充当潜在的介导物，中介比例为 3.9%（95% CI，0.6%-6.9%）。
总之，我们的研究确立了哮喘和 UC 之间的因果关系，其中 IL-18 起了很小的作用。然而，哮喘对 UC 影响的主要因素尚不清楚。未来的研究应集中于确定其他潜在的介导物。在临床实践中，重要的是要更加关注哮喘患者的肠道病变。
