Department of Radiology, Tianjin Key Laboratory of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin, 300052, China.
Institute of Mental Health, Tianjin Anding Hospital, Mental Health Center of Tianjin Medical University, Tianjin, 300222, China.
J Headache Pain. 2024 Oct 28;25(1):186. doi: 10.1186/s10194-024-01896-y.
Previous studies have shown that migraines are associated with brain structural changes. However, the causal relationships between these changes and migraine, as well as its subtypes, migraine with aura (MA) and migraine without aura (MO), remain largely unclear.
We utilized genome-wide association study (GWAS) summary statistics from European cohorts for 2,347 cortical structural magnetic resonance imaging (MRI) phenotypes, derived from both T1-weighted and diffusion tensor imaging scans (n = 36,663), with migraine and its subtypes (n = 147,970-375,752). Cortical phenotypes included both macrostructural (e.g., cortical thickness, surface area) and microstructural (e.g., fractional anisotropy, mean diffusivity) features. Genetic correlations were first assessed to identify significant associations, followed by bidirectional Mendelian randomization (MR) analyses to determine causal relationships between these brain phenotypes and migraine, as well as its subtypes (MA and MO). Sensitivity analyses were applied to ensure the robustness of the results.
Genetic correlation analysis identified 510 significant associations between cortical structural phenotypes and migraine across 401 distinct traits. Forward MR analysis revealed nine significant causal effects of cortical structural changes on migraine risk. Specifically, increased cortical thickness and local gyrification index in specific cortical regions were associated with a decreased risk of overall migraine, MA, and MO, while intracellular volume fraction and orientation diffusion index in specific regions increased the risk of MA and MO. Reverse MR analysis demonstrated that MA causally increased mean diffusivity in the insular and frontal opercular cortex. Sensitivity analyses confirmed the robustness of these findings, with no evidence of horizontal pleiotropy or heterogeneity.
This study identifies causal relationships between cortical neuroimaging phenotypes and migraine, highlighting potential biomarkers for migraine diagnosis, treatment, and prevention.
先前的研究表明，偏头痛与大脑结构变化有关。然而，这些变化与偏头痛及其亚型（有先兆偏头痛和无先兆偏头痛）之间的因果关系，以及偏头痛与大脑结构变化之间的因果关系，在很大程度上仍不清楚。
我们利用了来自欧洲队列的全基因组关联研究（GWAS）汇总统计数据，这些数据来自 T1 加权和弥散张量成像扫描的 2347 个皮质结构磁共振成像（MRI）表型（n=36663），其中包括偏头痛及其亚型（n=147970-375752）。皮质表型包括宏观结构（例如皮质厚度、表面积）和微观结构（例如各向异性分数、平均弥散度）特征。首先评估遗传相关性以确定显著关联，然后进行双向孟德尔随机化（MR）分析，以确定这些大脑表型与偏头痛及其亚型（有先兆偏头痛和无先兆偏头痛）之间的因果关系。还进行了敏感性分析以确保结果的稳健性。
遗传相关分析确定了皮质结构表型与偏头痛之间的 401 个不同特征之间的 510 个显著关联。正向 MR 分析显示，皮质结构变化对偏头痛风险有 9 个显著的因果影响。具体而言，特定皮质区域的皮质厚度和局部脑回指数增加与整体偏头痛、有先兆偏头痛和无先兆偏头痛的风险降低有关，而特定区域的细胞内体积分数和各向异性指数增加则增加了有先兆偏头痛和无先兆偏头痛的风险。反向 MR 分析表明，有先兆偏头痛导致岛叶和额眶皮质的平均弥散度增加。敏感性分析证实了这些发现的稳健性，没有水平多效性或异质性的证据。
这项研究确定了皮质神经影像学表型与偏头痛之间的因果关系，强调了偏头痛诊断、治疗和预防的潜在生物标志物。
