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

Chencheng Ma; Weiwei Zhang; Lei Mao; Guangjian Zhang; Yuqi Shen; Hanxiao Chang; Xiupeng Xu; Huiru Jin; Zheng Li; Hua Lu

doi:10.1186/s12883-023-03288-2

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

BMC Neurol. 2023 Jul 15;23(1):269. doi: 10.1186/s12883-023-03288-2.

Authors

Chencheng Ma^#^{1

2}, Weiwei Zhang^#³, Lei Mao^{1

2}, Guangjian Zhang^{1

2}, Yuqi Shen^{1

2}, Hanxiao Chang^{1

2}, Xiupeng Xu^{1

2}, Huiru Jin⁴, Zheng Li^{5

6}, Hua Lu^{7

8}

Affiliations

¹ Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
² Department of Neurosurgery, Jiangsu Province Hospital, Nanjing, Jiangsu Province, China.
³ Department of Ophthalmology, Third Medical Center of Chinese, PLA General Hospital, Beijing, China.
⁴ Department of Infectious Diseases, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
⁵ Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China. lznjmu@163.com.
⁶ Department of Neurosurgery, Jiangsu Province Hospital, Nanjing, Jiangsu Province, China. lznjmu@163.com.
⁷ Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China. luhua@njmu.edu.cn.
⁸ Department of Neurosurgery, Jiangsu Province Hospital, Nanjing, Jiangsu Province, China. luhua@njmu.edu.cn.

^# Contributed equally.

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: Causality; Gut microbiome; Intracranial aneurysm; Mendelian randomization; cerebrovascular disease.

MeSH terms

Gastrointestinal Microbiome* / genetics
Genome-Wide Association Study
Humans
Intracranial Aneurysm* / genetics
Mendelian Randomization Analysis
Odds Ratio
Polymorphism, Single Nucleotide / genetics

Abstract

MeSH terms

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