Department of Epidemiology, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Ministry of Education (MOE) Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College of Soochow University, Suzhou 215123, China.
Department of Medical Imaging, The Affiliated Guangji Hospital of Soochow University, Suzhou 215137, China.
Cereb Cortex. 2023 Oct 14;33(21):10848-10857. doi: 10.1093/cercor/bhad329.
Brian imaging-derived phenotypes (IDPs) have been suggested to be associated with ischemic stroke, but the causality between them remains unclear. In this bidirectional two-sample Mendelian randomization (MR) study, we explored the potential causal relationship between 461 imaging-derived phenotypes (n = 33,224, UK Biobank) and ischemic stroke (n = 34,217 cases/406,111 controls, Multiancestry Genome-Wide Association Study of Stroke). Forward MR analyses identified five IDPs associated with ischemic stroke, including mean diffusivity (MD) in the right superior fronto-occipital fasciculus (1.22 [95% CI, 1.11-1.34]), MD in the left superior fronto-occipital fasciculus (1.30 [1.17-1.44]), MD in the anterior limb of the right internal capsule (1.36 [1.22-1.51]), MD in the right anterior thalamic radiation (1.17 [1.09-1.26]), and MD in the right superior thalamic radiation (1.23 [1.11-1.35]). In the reverse MR analyses, ischemic stroke was identified to be associated with three IDPs, including high isotropic or free water volume fraction in the body of corpus callosum (beta, 0.189 [95% confidence interval, 0.107-0.271]), orientation dispersion index in the pontine crossing tract (0.175 [0.093-0.257]), and volume of the third ventricle (0.219 [0.138-0.301]). This bidirectional two-sample MR study suggested five predictors and three diagnostic markers for ischemic stroke at the brain-imaging level. Further studies are warranted to replicate our findings and clarify underlying mechanisms.
脑影像衍生表型（IDPs）与缺血性脑卒中有关，但它们之间的因果关系尚不清楚。在这项双向两样本孟德尔随机化（MR）研究中，我们探讨了 461 种脑影像衍生表型（n=33224，英国生物库）与缺血性脑卒中（n=34217 例/406111 例对照，多祖先全基因组关联研究中风）之间潜在的因果关系。正向 MR 分析确定了与缺血性脑卒中相关的五个 IDP，包括右侧额枕上束的平均弥散度（MD）（1.22[95%CI，1.11-1.34]）、左侧额枕上束的 MD（1.30[1.17-1.44]）、右侧内囊前肢的 MD（1.36[1.22-1.51]）、右侧前丘脑辐射的 MD（1.17[1.09-1.26]）和右侧上丘脑辐射的 MD（1.23[1.11-1.35]）。在反向 MR 分析中，缺血性脑卒中与三个 IDP 相关，包括胼胝体体部的各向同性或游离水体积分数较高（β，0.189[95%置信区间，0.107-0.271]）、脑桥交叉束的各向异性弥散指数（0.175[0.093-0.257]）和第三脑室体积（0.219[0.138-0.301]）。这项双向两样本 MR 研究表明，在脑成像水平上，缺血性脑卒中有五个预测因子和三个诊断标志物。需要进一步的研究来复制我们的发现并阐明潜在的机制。
