Graduate School of Hebei Medical University, Shijiazhuang, China.
Graduate School of Hebei North University, Zhangjiakou, China.
Sci Rep. 2024 Sep 28;14(1):22504. doi: 10.1038/s41598-024-74023-1.
The correlation between diverticular disease of the intestine and cirrhosis is well-established, however, the presence of a genetic causal link between the two conditions remains uncertain. The study employed a two-sample Mendelian randomization approach utilizing the most recent genome-wide association study (GWAS) data to investigate the correlation between diverticulosis and liver cirrhosis. The primary analysis was conducted using the Inverse Variance Weighted (IVW) method, and was further corroborated by an array of statistical techniques including MR-Egger, Weighted Median, Weighted Mode, cML-MA, ConMix, MR-RAPS, and DIVW to ensure robustness and reliability of the findings.Heterogeneity was evaluated using Cochran's Q test, horizontal pleiotropy was assessed through MR-Egger regression, and leave-one-out analyses were performed to validate the causal relationships. The IVW method found that diverticular disease significantly reduces the risk of cirrhosis (OR = 0.849, 95% CI: 0.743-0.971, P = 0.016). All models had P-values < 0.05 and negative β values. MR-Egger regression showed no horizontal pleiotropy (P = 0.215), confirming SNP reliability. Cochran's Q values for IVW and MR-Egger were 57.23 (P = 0.39) and 55.62 (P = 0.41), indicating no heterogeneity. Sensitivity analysis with the leave-one-out method validated the robustness of the results. This research utilizes Mendelian randomization to illustrate the potential protective role of diverticulosis against liver cirrhosis. The results are analyzed through the lenses of gut microbiota and cytokine levels, providing new perspectives that may inform clinical approaches to diagnosis and treatment.
肠憩室病与肝硬化之间的相关性已得到充分证实，然而，这两种疾病之间是否存在遗传因果关系尚不确定。本研究采用两样本孟德尔随机化方法，利用最新的全基因组关联研究（GWAS）数据，探讨憩室病与肝硬化之间的相关性。主要分析采用逆方差加权（IVW）方法，并通过一系列统计技术（包括 MR-Egger、加权中位数、加权众数、cML-MA、ConMix、MR-RAPS 和 DIVW）进行了进一步验证，以确保研究结果的稳健性和可靠性。使用 Cochran's Q 检验评估异质性，通过 MR-Egger 回归评估水平性多效性，并进行逐一删除分析以验证因果关系。IVW 方法发现，憩室病显著降低了肝硬化的风险（OR=0.849，95%CI：0.743-0.971，P=0.016）。所有模型的 P 值均<0.05，且β值为负。MR-Egger 回归未显示水平性多效性（P=0.215），证实了 SNP 的可靠性。IVW 和 MR-Egger 的 Cochran's Q 值分别为 57.23（P=0.39）和 55.62（P=0.41），表明无异质性。采用逐一删除法进行敏感性分析验证了结果的稳健性。本研究利用孟德尔随机化阐明了憩室病对肝硬化的潜在保护作用。通过肠道微生物群和细胞因子水平的视角分析结果，为诊断和治疗提供了新的思路。
