Department of Neurology, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, Nanjing, China.
Department of Neurology, Jinling Hospital, Affiliated Medical School of Nanjing University, Nanjing, China.
Eur J Neurol. 2022 May;29(5):1534-1537. doi: 10.1111/ene.15277. Epub 2022 Feb 20.
The association between non-alcoholic fatty liver disease (NAFLD) and the risk of stroke is heterogeneous. Therefore, we aimed to examine any potential causal relationship between these two traits through Mendelian randomization.
The genetic instruments associated with NAFLD were selected from a large genome-wide association study in individuals of European ancestry (1483 cases and 17,781 controls, replicated in 559 cases and 945 controls). The genetic associations for stroke (40,585 cases and 406,111 controls) and ischemic stroke (34,217 cases and 406,111 controls) were selected from the MEGASTROKE consortium of European ancestry participants. The causal effects on ischemic stroke subtypes, including large artery atherosclerosis (LAA) (4373 cases and 146,392 controls), small vessel occlusion (SVO) (5386 cases and 192,662 controls), and cardioembolic stroke (7193 cases and 204,570 controls), were also analyzed. The inverse variant weighted method was performed to obtain the casual estimates. Heterogeneity and pleiotropy of individual single nucleotide polymorphisms were also tested for the robustness of the results.
NAFLD was not associated with stroke (odds ratio [OR] 1.015; 95% confidence interval [CI] 0.996-1.034; p = 0.121) and ischemic stroke (OR 1.017; 95% CI 0.997-1.037; p = 0.092). Regarding ischemic stroke subtypes, there were positive causal inferences on LAA (OR 1.065; 95% CI 1.004-1.129; p = 0.037) and SVO (OR 1.058; 95% CI 1.003-1.116; p = 0.037), while it was not significant for cardioembolic stroke (OR 1.026; 95% CI 0.983-1.071; p = 0.243).
This study suggests that the potential causal effect of NAFLD on ischemic stroke may be confined to the LAA and SVO subtypes.
非酒精性脂肪性肝病（NAFLD）与中风风险之间的关联存在异质性。因此，我们旨在通过孟德尔随机化研究来检验这两种特征之间是否存在潜在的因果关系。
从欧洲血统个体的全基因组关联研究中选择与 NAFLD 相关的遗传工具（1483 例病例和 17781 例对照，在 559 例病例和 945 例对照中得到复制）。从欧洲血统的 MEGASTROKE 联盟参与者中选择与中风（40585 例病例和 406111 例对照）和缺血性中风（34217 例病例和 406111 例对照）相关的遗传关联。还分析了缺血性中风亚型（包括大动脉粥样硬化（LAA）（4373 例病例和 146392 例对照）、小血管闭塞（SVO）（5386 例病例和 192662 例对照）和心源性栓塞性中风（7193 例病例和 204570 例对照）的因果作用。使用逆变异加权法获得因果估计值。还测试了个体单核苷酸多态性的异质性和多效性，以验证结果的稳健性。
NAFLD 与中风（比值比[OR]1.015；95%置信区间[CI]0.996-1.034；p=0.121）和缺血性中风（OR1.017；95%CI0.997-1.037；p=0.092）无关。关于缺血性中风亚型，LAA（OR1.065；95%CI1.004-1.129；p=0.037）和 SVO（OR1.058；95%CI1.003-1.116；p=0.037）存在阳性因果推断，而心源性栓塞性中风无显著相关性（OR1.026；95%CI0.983-1.071；p=0.243）。
本研究表明，NAFLD 对缺血性中风的潜在因果作用可能仅限于 LAA 和 SVO 亚型。
