Two-Sample Bidirectional Mendelian Randomization Study With Causal Association Between Metabolic Syndrome and Cerebral Aneurysm

IF 2.7 3区心理学 Q2 BEHAVIORAL SCIENCES

Brain and Behavior Pub Date : 2025-03-04 DOI:10.1002/brb3.70396

Yu Li, Kai Zhao

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Abstract

Background

We used a two-sample mendelian randomization (MR) method to comprehensively investigate the causality of metabolic syndrome (MetS) or its components, including MetS, triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), fasting blood glucose (FBG), waist circumference (WC), and hypertension (HP), with cerebral aneurysm including nonruptured and ruptured aneurysmal subarachnoid hemorrhage (SAH).

Methods

By leveraging large-scale genome-wide association study (GWAS) summary statistics of MetS or its components and cerebral aneurysm (nonruptured and SAH) from European, MR, reverse-direction MR, and sensitivity analysis were utilized to quantify the genetic correlations and causal relationships. In addition, we adjusted for multiple comparisons using the false discovery rate (FDR) correction.

Results

Two-sample MR analysis showed that HP was a risk factor for cerebral aneurysm (nonruptured and SAH) with odds ratio (OR) of 58.959 (95% confidence interval [95% CI] = 12.073–287.920, p < 0.001, q < 0.001), and 32.290 (95% CI = 5.615–185.671, p < 0.001, q < 0.001), respectively. HDL-C (OR = 0.836, 95% CI = 0.728–0.960, p = 0.011, q = 0.039) and FBG (OR = 0.626, 95% CI = 0.426–0.919, p = 0.017, q = 0.039) were negatively correlated with cerebral aneurysm (nonruptured). The HDL-C result was inconsistent after adjusting for TG and LDL-C by multivariable MR analysis. In reverse MR analysis, we found that there was no statistical causal association between cerebral aneurysm (nonruptured) and MetS or its components. Genetic liability to cerebral aneurysm (SAH) was inversely associated with HDL-C and FBG but was not associated with others, however, sensitivity analysis showed that few instrumental variables made a big difference.

Conclusions

Genetically determined elevated FBG level reduces the risk of cerebral aneurysm (nonruptured). However, hypertension increases the risk of cerebral aneurysm (nonruptured and SAH).

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代谢综合征与脑动脉瘤因果关系的双样本双向孟德尔随机研究

本研究采用双样本孟德尔随机化（MR）方法，全面研究代谢综合征（MetS）及其组成部分的因果关系，包括MetS、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、空腹血糖（FBG）、腰围（WC）和高血压（HP）。脑动脉瘤包括未破裂和破裂的动脉瘤性蛛网膜下腔出血（SAH）。方法利用大规模全基因组关联研究（GWAS），汇总统计MetS或其组成部分与欧洲脑动脉瘤（未破裂和SAH）、MR、反向MR和敏感性分析来量化遗传相关性和因果关系。此外，我们使用错误发现率（FDR）校正对多个比较进行了调整。结果双样本磁共振分析显示，HP是脑动脉瘤（未破裂和SAH）的危险因素，优势比（OR）为58.959(95%可信区间[95% CI] = 12.073-287.920, p <；0.001, q <；0.001), 32.290 (95% CI = 5.615-185.671, p <；0.001, q <；分别为0.001)。HDL-C （OR = 0.836, 95% CI = 0.728-0.960, p = 0.011, q = 0.039）和FBG （OR = 0.626, 95% CI = 0.426-0.919, p = 0.017, q = 0.039）与脑动脉瘤（未破裂）呈负相关。多变量MR分析校正TG和LDL-C后，HDL-C结果不一致。在反向MR分析中，我们发现脑动脉瘤（未破裂）与MetS或其组成部分之间没有统计学上的因果关系。脑动脉瘤（SAH）的遗传易感性与HDL-C和FBG呈负相关，但与其他因素无关，然而，敏感性分析显示，一些工具变量产生了很大的差异。结论基因决定的FBG水平升高可降低脑动脉瘤（未破裂）的风险。然而，高血压增加了脑动脉瘤（未破裂和SAH）的风险。

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来源期刊

Brain and Behavior BEHAVIORAL SCIENCES-NEUROSCIENCES

CiteScore

5.30

自引率

0.00%

发文量

352

审稿时长

14 weeks

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