Xu Ran, Hu Xinzhi, Wang Tao, Yang Yutong, Jiang Nan, Luo Jichang, Zhang Xiao, Patel Aman B, Dmytriw Adam A, Jiao Liqun
Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China.
China International Neuroscience Institute (China-INI), Beijing, China.
Front Neurol. 2022 Apr 11;13:804851. doi: 10.3389/fneur.2022.804851. eCollection 2022.
In recent years, metabolic syndrome has risen in prevalence and brought a heavy disease burden to modern society. As the representative aspect of metabolic syndrome, obesity has been shown to be related to an increased risk of stroke. Given that visceral adipose tissue (VAT) forms the fundamental basis of central obesity, we sought to explore a causal relationship between VAT and stroke by using mendelian randomization (MR) methods.
Based on two large genome-wide association studies (GWAS) including 325,153 and 35,762 cases of VAT and stroke, respectively, we conducted a MR study which has the inherent advantage of reducing the noise of confounding and reverse causation.
VAT had a significant causal association with ischemic stroke (OR, per 1kg increase in VAT mass, 1.30; 95% CI, 1.18 ~ 1.45; = 5.87E-07) as opposed to intracranial hemorrhage (ICH) (OR, 1.15; 95% CI, 0.70 ~ 1.88, = 5.81E-01) as evaluated with inverse-variance weighting (IVW). Regarding subtypes of ischemic stroke, there was a significant causal effect for cardioembolic stroke (OR, 1.34; 95% CI, 1.13 ~ 1.58, = 8.07E-04), and potential causal effect for small-vessel stroke (OR, 1.32; 95% CI, 1.06 ~ 1.65, = 1.39E-02) and large-artery atherosclerotic stroke (OR, 1.33; 95% CI, 1.03 ~ 1.70, = 2.59E-02).
This study provides potential evidence for a causal role of VAT in ischemic stroke and could suggest novel genetical therapeutic strategies for distinct subtypes of ischemic stroke.
近年来，代谢综合征的患病率不断上升，给现代社会带来了沉重的疾病负担。作为代谢综合征的典型表现，肥胖已被证明与中风风险增加有关。鉴于内脏脂肪组织（VAT）是中心性肥胖的基本基础，我们试图通过孟德尔随机化（MR）方法探索VAT与中风之间的因果关系。
基于两项大型全基因组关联研究（GWAS），分别纳入了325,153例VAT病例和35,762例中风病例，我们进行了一项MR研究，该研究具有减少混杂和反向因果关系噪声的固有优势。
与颅内出血（ICH）相反，VAT与缺血性中风存在显著的因果关联（每增加1kg VAT质量，OR为1.30；95%CI为1.181.45；P = 5.87E-07）（OR为1.15；95%CI为0.701.88，P = 5.81E-01），采用逆方差加权（IVW）评估。关于缺血性中风的亚型，心源性栓塞性中风存在显著的因果效应（OR为1.34；95%CI为1.131.58，P = 8.07E-04），小血管性中风和大动脉粥样硬化性中风存在潜在的因果效应（OR分别为1.32；95%CI为1.061.65，P = 1.39E-02；OR为1.33；95%CI为1.03~1.70，P = 2.59E-02）。
本研究为VAT在缺血性中风中的因果作用提供了潜在证据，并可能为缺血性中风的不同亚型提出新的基因治疗策略。
