Tan Jiacong, Zhu Huaxin, Zeng Yanyang, Li Jiawei, Zhao Yeyu, Li Meihua
Department of Neurosurgery, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 17 Yongwaizheng Street, Nanchang, 330006, Jiangxi, China.
Neuroscience. 2025 Feb 6;566:9-16. doi: 10.1016/j.neuroscience.2024.12.034. Epub 2024 Dec 19.
The aim of this study was to assess the potential causal relationship between lifestyle factors and intracranial aneurysms (IAs) using a two-sample Mendelian randomization (MR) approach. The study used a pooled dataset from a genome-wide association study that covered information on 24 lifestyle factors, intracranial aneurysm cases, subarachnoid hemorrhage, and unruptured aneurysms. Five MR methods were applied for analysis by selecting single nucleotide polymorphisms as instrumental variables, with the inverse variance weighting method as the main method. To ensure the stability of the results, horizontal multiple validity tests, sensitivity analyses, and inverse MR were performed, and genetically determined exposure factors were adjusted by multivariate MR. Several lifestyle factors were found to have a significant genetic causal effect on the occurrence and development of intracranial aneurysms. For example, lamb intake, smoking initiation, number of cigarettes smoked per day, length of television viewing, and fatigue were identified as genetic risk factors and strongly associated with aneurysm rupture, whereas red wine intake showed some genetic protection against intracranial aneurysms and similarly affected aneurysm rupture. Sensitivity analyses and inverse MR verified the robustness of these results. After adjusting for exposure factors, multivariate MR confirmed daily smoking and smoking initiation as risk factors for intracranial aneurysms, unruptured aneurysms, and subarachnoid hemorrhage, whereas red wine intake was a genetically protective factor against intracranial aneurysms and subarachnoid hemorrhage. This MR analysis revealed a genetic causal link between specific lifestyle factors and intracranial aneurysms, emphasizing the need for further studies to confirm these findings and explore their mechanisms.
本研究旨在采用两样本孟德尔随机化（MR）方法评估生活方式因素与颅内动脉瘤（IA）之间的潜在因果关系。该研究使用了一个全基因组关联研究的汇总数据集，其中涵盖了24种生活方式因素、颅内动脉瘤病例、蛛网膜下腔出血和未破裂动脉瘤的信息。通过选择单核苷酸多态性作为工具变量，应用五种MR方法进行分析，其中以逆方差加权法为主要方法。为确保结果的稳定性，进行了横向多重有效性检验、敏感性分析和反向MR，并通过多变量MR对基因确定的暴露因素进行了调整。发现几种生活方式因素对颅内动脉瘤的发生和发展具有显著的遗传因果效应。例如，羊肉摄入量、开始吸烟、每日吸烟量、看电视时长和疲劳被确定为遗传风险因素，与动脉瘤破裂密切相关，而饮用红酒对颅内动脉瘤具有一定的遗传保护作用，且同样影响动脉瘤破裂。敏感性分析和反向MR验证了这些结果的稳健性。在调整暴露因素后，多变量MR证实每日吸烟和开始吸烟是颅内动脉瘤、未破裂动脉瘤和蛛网膜下腔出血的风险因素，而饮用红酒是针对颅内动脉瘤和蛛网膜下腔出血的遗传保护因素。这项MR分析揭示了特定生活方式因素与颅内动脉瘤之间的遗传因果联系，强调需要进一步研究以证实这些发现并探索其机制。
