肠道微生物组与颅内动脉瘤风险的关联：一项孟德尔随机化研究。
Association of gut microbiome with risk of intracranial aneurysm: a mendelian randomization study.
机构信息
Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
Department of Neurosurgery, Jiangsu Province Hospital, Nanjing, Jiangsu Province, China.
出版信息
BMC Neurol. 2023 Jul 15;23(1):269. doi: 10.1186/s12883-023-03288-2.
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) single nucleotide polymorphisms (SNPs) as instrumental variables (IVs). Then, we selected the locus-wide significant (P < 1 × 10) 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.
目的
利用两样本 Mendelian 随机化（MR）方法研究与肠道微生物组相关的遗传变异与颅内动脉瘤（IA）风险之间的潜在因果关系。
方法
我们进行了两组 MR 分析。首先，我们选择全基因组统计学显著（P < 5×10）的单核苷酸多态性（SNPs）作为工具变量（IVs）。然后，我们选择局域显著（P < 1×10）的 SNPs 作为另一组分析的 IVs，以得出更全面的结论。肠道微生物组遗传关联估计值来自对 18473 个人的全基因组关联研究（GWAS）。IA 的汇总水平统计数据来自包含 7495 例病例和 71934 例对照的 79429 个人。
结果
基于局域显著性水平，逆方差加权（IVW）显示梭菌（OR：2.60；95%置信区间（CI）：1.00-6.72，P=0.049）、 Adlercreutzia（OR：1.81；95%CI：1.10-2.99，P=0.021）和 Victivallis（OR：1.38；95%CI：1.01-1.88，P=0.044）与未破裂颅内动脉瘤（UIA）的风险呈正相关；MR 加权中位数结果显示 Oscillospira（OR：0.37；95%CI：0.17-0.84，P=0.018）与 UIA 的风险呈负相关，Sutterella（OR：1.84；95%CI：1.04-3.23，P=0.035）与 UIA 的风险呈正相关；MR-Egger 方法分析表明，Paraprevotella（OR：0.32；95%CI：0.13-0.80，P=0.035）与 UIA 的风险呈负相关，Rhodospirillaceae（OR：13.39；95%CI：1.44-124.47，P=0.048）与 UIA 的风险呈正相关。结果表明，根据全基因组统计学显著性阈值，Streptococcus（OR：5.19；95%CI：1.25-21.56；P=0.024）和 Peptostreptococcaceae（OR：4.92；95%CI：1.32-18.32；P=0.018）可能会增加 UIA 的风险。
结论
本 MR 分析表明，肠道微生物组成与 IA 之间存在有益或有害的因果关系。
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