College of Basic Medical Sciences, Dali University, 22 Wanhua Road, Dali 671000, Yunnan, China.
Department of Pathology, The First Affiliated Hospital of Dali University, 32 Jiashibo Road, Dali 671000, Yunnan, China.
Cereb Cortex. 2024 Aug 1;34(8). doi: 10.1093/cercor/bhae342.
Metabolic syndrome exhibits associations with diverse neurological disorders, and its potential influence on the cerebral cortex may be one of the many potential factors contributing to these adverse outcomes. In this study, we aimed to investigate the causal relationship between metabolic syndrome and changes in cerebral cortex structure using Mendelian randomization analysis. Genome-wide association study data for the 5 components of metabolic syndrome were obtained from individuals of European descent in the UK Biobank. Genome-wide association study data for 34 known cortical functional regions were sourced from the ENIGMA Consortium. Data on Alzheimer's disease, major depression, and anxiety disorder were obtained from the IEU Open genome-wide association study database. The causal links between metabolic syndrome elements and cerebral cortex architecture were evaluated using inverse variance weighting, Mendelian randomization-Egger, and weighted median techniques, with inverse variance weighting as the primary method. Inverse variance weighting, Mendelian randomization Egger, weighted median, simple mode, and weighted mode methods were employed to assess the relationships between metabolic syndrome and neurological diseases (Alzheimer's disease, major depression, and anxiety disorder). Outliers, heterogeneity, and pleiotropy were assessed using Cochran's Q test, MR-PRESSO, leave-one-out analysis, and funnel plots. Globally, no causal link was found between metabolic syndrome and overall cortical thickness or surface area. However, regionally, metabolic syndrome may influence the surface area of specific regions, including the caudal anterior cingulate, postcentral, posterior cingulate, rostral anterior cingulate, isthmus cingulate, superior parietal, rostral middle frontal, middle temporal, insula, pars opercularis, cuneus, and inferior temporal. It may also affect the thickness of the medial orbitofrontal, caudal middle frontal, paracentral, superior frontal, superior parietal, and supramarginal regions. These findings were nominally significant and withstood sensitivity analyses, showing no substantial heterogeneity or pleiotropy. Furthermore, we found an association between metabolic syndrome and the risk of Alzheimer's disease, major depression, and anxiety disorder. This study suggests a potential association between metabolic syndrome and changes in cerebral cortex structure, which may underlie certain neurological disorders. Furthermore, we found an association between metabolic syndrome and the risk of Alzheimer's disease, major depression, and anxiety disorder. Early diagnosis of metabolic syndrome holds significance in preventing these neurological disorders.
代谢综合征与多种神经退行性疾病有关，其对大脑皮层的潜在影响可能是导致这些不良后果的众多潜在因素之一。在这项研究中，我们旨在使用孟德尔随机化分析来研究代谢综合征与大脑皮层结构变化之间的因果关系。代谢综合征的 5 个组成部分的全基因组关联研究数据来自英国生物库中的欧洲血统个体。34 个已知大脑皮层功能区域的全基因组关联研究数据来自 ENIGMA 联盟。阿尔茨海默病、重度抑郁症和焦虑症的数据来自 IEU 开放全基因组关联研究数据库。使用逆方差加权、孟德尔随机化 Egger 和加权中位数技术评估代谢综合征各组成部分与大脑皮层结构之间的因果关系，逆方差加权是主要方法。使用逆方差加权、孟德尔随机化 Egger、加权中位数、简单模式和加权模式方法评估代谢综合征与神经退行性疾病（阿尔茨海默病、重度抑郁症和焦虑症）之间的关系。使用 Cochran's Q 检验、MR-PRESSO、遗漏值分析和漏斗图评估离群值、异质性和多效性。总体而言，代谢综合征与整体皮层厚度或表面积之间没有发现因果关系。然而，在区域层面上，代谢综合征可能会影响特定区域的表面积，包括后扣带回、中央后回、后扣带回、前扣带回、岛盖部、楔前叶和颞中回。它也可能影响内侧眶额回、中额下回、旁中央小叶、额上回、顶叶上回和缘上回的厚度。这些发现具有名义上的显著性，并经受住了敏感性分析，表明没有实质性的异质性或多效性。此外，我们发现代谢综合征与阿尔茨海默病、重度抑郁症和焦虑症的风险之间存在关联。这项研究表明代谢综合征与大脑皮层结构变化之间可能存在潜在的关联，这可能是某些神经退行性疾病的基础。此外，我们发现代谢综合征与阿尔茨海默病、重度抑郁症和焦虑症的风险之间存在关联。早期诊断代谢综合征对于预防这些神经退行性疾病具有重要意义。
