肠道菌群与POAG因果关系的两样本孟德尔随机化研究

Mendelian randomization study on the causal relationship between gut microbiota and primary open angle glaucoma

摘要:

目的：利用两样本孟德尔随机化(MR)的研究方法探究肠道菌群(GM)与原发性开角型青光眼(POAG)的潜在因果关系。

方法：利用英国布里斯托尔大学的GM的全基因组关联研究数据(GWAS)作为暴露和IEU Open GWAS数据库中POAG的GWAS数据作为结局，采用逆方差加权(IVW)、MR Egger、加权中位数(WM)、Simple Mode、Weighted Mode方法分析POAG与GM之间存在的潜在关系，其中IVW为主要分析方法。敏感性分析检测该MR分析结果是否可靠。

结果：IVW分析显示，Butyrivibrio(OR=1.170，95%CI：1.057-1.295，P=0.002)、Howardella(OR=1.188，95%CI：1.043-1.355，P=0.010)、LachnospiraceaeUCG001(OR=1.229，95%CI：1.016-1.485，P=0.033)增加了POAG的发病风险； 而Candidatus Soleaferrea(OR=0.810，95%CI：0.670-0.981，P=0.031)、Ruminococcustorquesgroup(OR=0.656，95%CI：0.453-0.950，P=0.026)、Ruminococcaceae-UCG013(OR=0.770，95%CI：0.598-0.990，P=0.041)降低了POAG的发病风险。敏感性分析结果表明以上结果不存在异质性和多效性，分析结果具有可靠性。

结论：GM与POAG存在潜在的因果关系，由于POAG具有致盲性，早期诊断和早期干预POAG的相关因素对该病的临床预后具有重要意义。

Abstract:

AIM: To investigate the potential causal relationship between gut microbiota(GM)and primary open-angle glaucoma(POAG)based on a two-sample Mendelian randomization(MR)analysis.

METHODS: The exposure data was derived from the Genome-Wide Association Studies(GWAS)of GM at the University of Bristol, while the outcome data for POAG was sourced from the MRC Integrative Epidemiology Unit(IEU)Open GWAS database. In this study, inverse variance weighted(IVW), MR Egger, weighted median(WM), Simple Mode, and Weighted Mode were analyzed to investigate the potential causal relationships between GM and POAG. IVW was used as the primary method for this study, and sensitivity analysis was conducted to assess the reliability of the MR analysis.

RESULTS: The IVW analysis revealed that Butyrivibrio(OR=1.170, 95%CI: 1.057-1.295, P=0.002), Howardella(OR=1.188, 95%CI: 1.043-1.355, P=0.010), and LachnospiraceaeUCG001(OR=1.229, 95%CI: 1.016-1.485, P=0.033)were correlated with the risk of POAG. Conversely, Candidatus Soleaferrea(OR=0.810, 95%CI: 0.670-0.981, P=0.031), Ruminococcustorquesgroup(OR=0.656, 95%CI: 0.453-0.950, P=0.026), and RuminococcaceaeUCG013(OR=0.770, 95%CI: 0.598-0.990, P=0.041)were protective factors for POAG. Sensitivity analysis showed that there were no heterogeneity and pleiotropy among the instrumental variables.

CONCLUSION: The MR study indicated a causal relationship between GM and POAG. Given the sight-threatening characteristic of POAG, early identification and intervention in the relative factors was significant for the prognosis of POAG.