肠道微生物与近视的因果联系——一项两样本孟德尔随机化分析

Causal Link between Gut Microbiota and Myopia—A Two-Sample Mendelian Randomization Analysis

摘要: 背景：肠道微生物群与近视之间的关系尚不明确。本研究通过两样本孟德尔随机化分析，探讨肠道微生物群落与近视发展之间的潜在因果联系。方法：本研究利用公开的全基因组关联研究(GWAS)数据进行孟德尔随机化分析。我们从MiBioGen联盟获取了肠道微生物组GWAS汇总统计数据，包括来自24个不同队列的18,340个样本。近视相关结果数据来自MRC IEU汇总的近视数据集，涵盖460,536名欧洲血统个体。以单核苷酸多态性(SNP)作为工具变量，重点关注F统计量大于10的SNP，以确保工具变量的强度。分析采用四种方法：逆方差加权(IVW)、MR-Egger回归、加权中位数方法和加权众数等技术。为探讨异质性和潜在多效性效应，我们进行了Cochran’s Q检验和MR-Egger截距检验。此外，通过留一法敏感性分析评估结果的稳健性。结果：逆方差加权(IVW)分析揭示了特定肠道微生物分类群与近视之间的关系。Lachnospiraceae_UCG-001显示出对近视的保护作用，比值比(OR)为0.993，95%置信区间(CI)为(0.987, 0.998)，P值为0.007，具有统计学意义。此外，厚壁菌门(Firmicutes)也显示出保护性关联，OR为0.994，95% CI为(0.989, 0.999)，P值为0.015。然而，双歧杆菌科(Bifidobacteriaceae)和食物谷菌科(Victivallaceae)被识别为近视的潜在危险因素，其OR分别为1.006和1.003，95% CI分别为(1.0001, 1.0113)和(1.0007, 1.0062)，P值分别为0.048和0.015。然而，反向孟德尔随机化分析未发现近视与肠道微生物之间存在显著的因果联系，且未观察到显著的异质性或多效性效应。结论：本分析表明，某些肠道微生物可能与近视存在因果关系，揭示了近视预防和治疗的潜在干预策略。

Abstract: Background: The relationship between gut microbiota and myopia remains uncertain. In this study, we conducted a two-sample Mendelian randomization analysis to investigate the potential causal connection between gut microbial communities and the development of myopic conditions. Methods: Our study utilized publicly available genomic data from genome-wide association studies (GWAS) to conduct Mendelian randomization analysis. We obtained gut microbiome GWAS summary statistics from the MiBioGen Consortium, which included 18,340 samples from 24 different cohorts. Data on myopia-related outcomes were taken from the MRC IEU’s integrated myopia dataset, which consisted of 460,536 individuals of European descent. Single nucleotide polymorphisms (SNPs) were used as instrumental variables, with a focus on those with an F-statistic greater than 10 to ensure strong instruments. Our analysis employed four different methods: inverse variance weighted (IVW), MR-Egger regression, the weighted median approach, and the weighted mode technique. To investigate heterogeneity and potential pleiotropic effects, we conducted Cochran’s Q test and MR-Egger intercept test. Furthermore, we assessed the robustness of our results through leave-one-out sensitivity analysis. Results: The inverse variance weighted (IVW) analysis revealed insights into the relationship between specific gut microbial taxa and myopia. Lachnospiraceae_UCG-001 was found to have a protective effect against myopia, with an odds ratio (OR) of 0.993, a 95% confidence interval (CI) of 0.987 to 0.998, and a statistically significant P-value of 0.007. Additionally, Firmicutes also showed a protective association, with an OR of 0.994, a 95% CI of 0.989 to 0.999, and a P-value of 0.015. On the other hand, Bifidobacteriaceae and Victivallaceae were identified as potential risk factors for myopia, with respective ORs of 1.006 and 1.003, 95% CIs from 1.0001 to 1.0113 and 1.0007 to 1.0062, and P-values of 0.048 and 0.015. However, the reverse Mendelian Randomization analysis did not find any significant causal links between myopia and this gut microbiota, and no significant heterogeneity or horizontal pleiotropy was observed. Conclusion: Our analysis suggests that certain gut microbiota may have a causal relationship with myopia, revealing potential intervention strategies for the prevention and treatment of myopia.