Effect of the gut microbiome in glaucoma risk from the causal perspective

Abstract

ObjectiveEvidence from observational studies has reported possible associations between the gut microbiome (GM) and glaucoma. However, the causal effect of GM on glaucoma risk remains to be determined.Methods and analysisWe conducted two-sample bidirectional Mendelian randomisation (MR) analyses to explore the causal association between GM and glaucoma. Genome-wide association study summary statistics of 196 GM taxa (n=18 340) and glaucoma (18 902 cases and 358 375 controls) were obtained from MiBioGen and FinnGen Consortium. Inverse variance weighted, MR-Egger, weighted median, weighted mode, Mendelian Randomisation Pleiotropy Residual Sum and Outlier, MR-Egger intercept and Cochran’s Q statistical analyses were used to supplement MR results and sensitivity analysis. An independent cohort from the Medical Research Council (MRC) Integrative Epidemiology Unit at the University of Bristol (MRC-IEU) Consortium (1715 cases and 359 479 controls) was used to validate causal effects.ResultsResults of the MR analysis suggested that the familyOxalobacteraceae(OR 0.900, 95% CI 0.843 to 0.961, p=0.002) and the genusEggerthella(OR 0.881, 95% CI 0.811 to 0.957, p=0.003) had a negative effect on glaucoma, whereas the genusBilophila(OR 1.202, 95% CI 1.074 to 1.346, p=0.001),LachnospiraceaeUCG010(OR 1.256, 95% CI 1.109 to 1.423, p=0.0003) andRuminiclostridium 9(OR 1.258, 95% CI 1.083 to 1.461, p=0.003) had a positive effect on glaucoma. Among these, the positive causal effect ofLachnospiraceaeUCG010(OR 1.002, 95% CI 1.000 to 1.004, p=0.033) on glaucoma was replicated in an independent cohort.ConclusionThis MR analysis from large population studies demonstrated the causal effect of GM on glaucoma risk and supported the role of GM in influencing glaucoma susceptibility.