Sun Jie, Xie Yingying, Li Tongli, Zhao Yunfei, Zhao Wenjin, Yu Zeyang, Wang Shaoying, Zhang Yujie, Xue Hui, Chen Yayuan, Sun Zuhao, Zhang Zhang, Liu Yaou, Zhang Ningnannan, Liu Feng
Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin 300052, China.
Department of Radiology, The First Affiliated Hospital of Fujian Medical University, Fujian 350005, China.
Brain Commun. 2024 Sep 11;6(5):fcae308. doi: 10.1093/braincomms/fcae308. eCollection 2024.
Multiple sclerosis and neuromyelitis optica spectrum disorder are two debilitating inflammatory demyelinating diseases of the CNS. Although grey matter alterations have been linked to both multiple sclerosis and neuromyelitis optica spectrum disorder in observational studies, it is unclear whether these associations indicate causal relationships between these diseases and grey matter changes. Therefore, we conducted a bidirectional two-sample Mendelian randomization analysis to investigate the causal relationships between 202 grey matter imaging-derived phenotypes (33 224 individuals) and multiple sclerosis (47 429 cases and 68 374 controls) as well as neuromyelitis optica spectrum disorder (215 cases and 1244 controls). Our results suggested that genetically predicted multiple sclerosis was positively associated with the surface area of the left parahippocampal gyrus ( = 0.018, = 2.383 × 10) and negatively associated with the volumes of the bilateral caudate (left: = -0.020, = 7.203 × 10; right: = -0.021, = 3.274 × 10) and putamen nuclei (left: = -0.030, = 2.175 × 10; right: = -0.024, = 1.047 × 10). In addition, increased neuromyelitis optica spectrum disorder risk was associated with an increased surface area of the left paracentral gyrus ( = 0.023, = 1.025 × 10). Conversely, no evidence was found for the causal impact of grey matter imaging-derived phenotypes on disease risk in the opposite direction. We provide suggestive evidence that genetically predicted multiple sclerosis and neuromyelitis optica spectrum disorder are associated with increased cortical surface area and decreased subcortical volume in specific regions. Our findings shed light on the associations of grey matter alterations with the risk of multiple sclerosis and neuromyelitis optica spectrum disorder.
多发性硬化症和视神经脊髓炎谱系障碍是中枢神经系统的两种使人衰弱的炎症性脱髓鞘疾病。尽管在观察性研究中灰质改变已与多发性硬化症和视神经脊髓炎谱系障碍相关联，但尚不清楚这些关联是否表明这些疾病与灰质变化之间存在因果关系。因此，我们进行了一项双向两样本孟德尔随机化分析，以研究202种源自灰质成像的表型（33224人）与多发性硬化症（47429例病例和68374例对照）以及视神经脊髓炎谱系障碍（215例病例和1244例对照）之间的因果关系。我们的结果表明，基因预测的多发性硬化症与左侧海马旁回的表面积呈正相关（=0.018，=2.383×10），与双侧尾状核的体积呈负相关（左侧：=-0.020，=7.203×10；右侧：=-0.021，=3.274×10）以及壳核（左侧：=-0.030，=2.175×10；右侧：=-0.024，=1.047×10）。此外，视神经脊髓炎谱系障碍风险增加与左侧中央旁回表面积增加相关（=0.023，=1.025×10）。相反，未发现源自灰质成像的表型对疾病风险有相反方向的因果影响的证据。我们提供了提示性证据，表明基因预测的多发性硬化症和视神经脊髓炎谱系障碍与特定区域皮质表面积增加和皮质下体积减小有关。我们的研究结果揭示了灰质改变与多发性硬化症和视神经脊髓炎谱系障碍风险之间的关联。
