孟德尔随机化
优势比
血脂
甘油三酯
内科学
混淆
脂蛋白
脂质体
脑出血
胆固醇
脂质代谢
内分泌学
血脂谱
瑞舒伐他汀
置信区间
医学
生物
蛛网膜下腔出血
基因型
生物化学
基因
遗传变异
作者
Youjia Qiu,Bingyi Song,Ziqian Yin,Menghan Wang,Yuansheng Tao,Minjia Xie,Aojie Duan,Zhouqing Chen,Ke Si,Zhong Wang
标识
DOI:10.1177/23969873241265019
摘要
Introduction: Different serum lipid and lipid-lowering agents are reported to be related to the occurrence of intracerebral aneurysm (IA). However, the causal relationship between them requires further investigation. Patients and methods: Mendelian randomization (MR) analysis was performed on IA and its subtypes by using instrumental variants associated with six serum lipids, 249 lipid metabolic traits, and 10 lipid-lowering agents that were extracted from the largest genome-wide association study. Phenome-wide MR analyses were conducted to identify potential phenotypes associated with significant lipid-lowering agents. Results: After multiple comparison adjustments ( p < 0.0083), genetically proxied triglyceride (TG) (odds ratio [OR] 1.25, 95% confidence interval [CI] 1.07–1.47, p = 0.005) and high-density lipoprotein cholesterol (HDL-C) levels (OR 0.93, 95% CI 0.89–0.98, p = 0.008) showed causal relationships with the risk of IA. Four lipid metabolic traits showed a causal relationship with the risk of IA ( p < 0.0002). As confirmed by drug target MR, the causal relationship between the HMGCR target and IA, HMGCR target and subarachnoid hemorrhage (SAH), ANGPTL3 target and SAH, CETP target, and SAH remained statistically significant after multiple adjustments ( p < 0.005). Additionally, phenome-wide MR did not identify other diseases linked to the significant lipid-lowering agent ( p < 6.39 × 10 −5 ). Discussion and conclusion: This study not only supports that serum lipids (TG and HDL-C) are associated with IA but also confirms the positive effect and absence of safety concerns of intervening HMGCR, ANGPTL3, and CETP targets in IA and its subtypes, opening new avenues for IA treatment.
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