Ma Chencheng, Zhang Weiwei, Mao Lei, Zhang Guangjian, Shen Yuqi, Chang Hanxiao, Xu Xiupeng, Li Zheng, Lu Hua
Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Department of Neurosurgery, Jiangsu Province Hospital, Nanjing, China.
Front Neurol. 2022 Sep 28;13:948989. doi: 10.3389/fneur.2022.948989. eCollection 2022.
To investigate the link between genetic variants associated with plasma homocysteine levels and risk of intracranial aneurysm (IA) using two-sample Mendelian randomization.
We used single-nucleotide polymorphisms associated with human plasma homocysteine levels as instrumental variables for the primary analysis in a genome-wide association study of 44,147 subjects of European ancestry. Summary-level statistics were obtained for 79,429 individuals, including 7,495 IA cases and 71,934 controls. To enhance validity, five different Mendelian randomization methods (MR-Egger, weighted median, inverse variance weighted, simple mode, and weighted mode) were used for the analyses.
The inverse variance weighted analysis method produced -values of 0.398 for aneurysmal subarachnoid hemorrhage [odds ratio (OR): 1.104; 95% confidence interval (CI): 0.878-1.387], 0.246 for IA (OR: 1.124; 95% CI: 0.923-1.368), and 0.644 for unruptured IA (OR: 1.126; 95% CI: 0.682-1.858). The MR-Egger analysis showed no association between IAs and homocysteine, with all > 0.05.
Using gene-related instrumental variables, the Mendelian randomization analyses demonstrated a lack of an association between plasma homocysteine levels and IAs or aneurysmal subarachnoid hemorrhage.
采用两样本孟德尔随机化方法研究与血浆同型半胱氨酸水平相关的基因变异与颅内动脉瘤（IA）风险之间的联系。
我们将与人类血浆同型半胱氨酸水平相关的单核苷酸多态性用作工具变量，对44147名欧洲血统受试者进行全基因组关联研究的初步分析。获得了79429名个体的汇总统计数据，包括7495例IA病例和71934例对照。为提高有效性，采用了五种不同的孟德尔随机化方法（MR-Egger、加权中位数、逆方差加权、简单模式和加权模式）进行分析。
逆方差加权分析方法得出，动脉瘤性蛛网膜下腔出血的P值为0.398[比值比（OR）：1.104；95%置信区间（CI）：0.878-1.387]，IA的P值为0.246（OR：1.124；95%CI：0.923-1.368），未破裂IA的P值为0.644（OR：1.126；95%CI：0.682-1.858）。MR-Egger分析显示IA与同型半胱氨酸之间无关联，所有P>0.05。
使用与基因相关的工具变量，孟德尔随机化分析表明血浆同型半胱氨酸水平与IA或动脉瘤性蛛网膜下腔出血之间缺乏关联。
