Association of gut microbiome with risk of intracranial aneurysm: a mendelian randomization study

Abstract

Abstract Objective To investigate the potential causal link between genetic variants associated with gut microbiome and risk of intracranial aneurysm (IA) using two-sample mendelian randomization (MR). Methods We performed two sets of MR analyses. At first, we selected the genome-wide statistical significant(P < 5 × 10–8) single nucleotide polymorphisms (SNPs) as instrumental variables (IVs). Then, we selected the locus-wide significant (P < 1 × 10–5) SNPs as IVs for the other set of analyses to obtain more comprehensive conclusions. Gut microbiome genetic association estimates were derived from a genome-wide association study (GWAS) of 18,473 individuals. Summary-level statistics for IA were obtained from 79,429 individuals, which included 7,495 cases and 71,934 controls. Results On the basis of locus-wide significance level, inverse variance weighted(IVW) showed that Clostridia [(odds ratio (OR): 2.60; 95% confidence interval (CI): 1.00—6.72, P = 0.049)], Adlercreutzia (OR: 1.81; 95% CI: 1.10—2.99, P = 0.021) and Victivallis (OR: 1.38; 95% CI: 1.01—1.88, P = 0.044) were positively related with the risk of unruptured intracranial aneurysm(UIA); Weighted median results of MR showed Oscillospira (OR: 0.37; 95% CI: 0.17—0.84, P = 0.018) was negatively with the risk of UIA and Sutterella (OR: 1.84; 95% CI: 1.04—3.23, P = 0.035) was positively related with the risk of UIA; MR-Egger method analysis indicated that Paraprevotella (OR: 0.32; 95% CI: 0.13—0.80, P = 0.035) was negatively with the risk of UIA and Rhodospirillaceae (OR: 13.39; 95% CI: 1.44—124.47, P = 0.048) was positively related with the risk of UIA. The results suggest that Streptococcus (OR: 5.19; 95% CI: 1.25—21.56; P = 0.024) and Peptostreptococcaceae (OR: 4.92; 95% CI: 1.32—18.32; P = 0.018) may increase the risk of UIA according to genome-wide statistical significance thresholds. Conclusion This MR analysis indicates that there exists a beneficial or detrimental causal effect of gut microbiota composition on IAs.

Keywords

• Mendelian randomization
• Intracranial aneurysm
• Gut microbiome
• cerebrovascular disease
• Causality