偏头痛与脑白质微观结构的因果关系：一项孟德尔随机化研究。
Causal relationships between migraine and microstructural white matter: a Mendelian randomization study.
机构信息
CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.
Department of Psychology, University of Chinese Academy of Sciences, Beijing, China.
出版信息
J Headache Pain. 2023 Feb 16;24(1):10. doi: 10.1186/s10194-023-01550-z.
BACKGROUND
Migraine is a disabling neurological disorder with the pathophysiology yet to be understood. The microstructural alteration in brain white matter (WM) has been suggested to be related to migraine in recent studies, but these evidence are observational essentially and cannot infer a causal relationship. The present study aims to reveal the causal relationship between migraine and microstructural WM using genetic data and Mendelian randomization (MR).
METHODS
We collected the Genome-wide association study (GWAS) summary statistics of migraine (48,975 cases / 550,381 controls) and 360 WM imaging-derived phenotypes (IDPs) (31,356 samples) that were used to measure microstructural WM. Based on instrumental variables (IVs) selected from the GWAS summary statistics, we conducted bidirectional two-sample MR analyses to infer bidirectional causal associations between migraine and microstructural WM. In forward MR analysis, we inferred the causal effect of microstructural WM on migraine by reporting the odds ratio (OR) that quantified the risk change of migraine for per 1 standard deviation (SD) increase of IDPs. In reverse MR analysis, we inferred the causal effect of migraine on microstructural WM by reporting the β value that represented SDs of changes in IDPs were caused by migraine.
RESULTS
Three WM IDPs showed significant causal associations (p < 3.29 × 10, Bonferroni correction) with migraine and were proved to be reliable via sensitivity analysis. The mode of anisotropy (MO) of left inferior fronto-occipital fasciculus (OR = 1.76, p = 6.46 × 10) and orientation dispersion index (OD) of right posterior thalamic radiation (OR = 0.78, p = 1.86 × 10) exerted significant causal effects on migraine. Migraine exerted a significant causal effect on the OD of left superior cerebellar peduncle (β = - 0.09, p = 2.78 × 10).
CONCLUSIONS
Our findings provided genetic evidence for the causal relationships between migraine and microstructural WM, bringing new insights into brain structure for the development and experience of migraine.
背景
偏头痛是一种致残性的神经系统疾病，其病理生理学尚未被完全理解。最近的研究表明，大脑白质（WM）的微观结构改变与偏头痛有关，但这些证据本质上是观察性的，不能推断出因果关系。本研究旨在利用遗传数据和孟德尔随机化（MR）揭示偏头痛和微观 WM 之间的因果关系。
方法
我们收集了偏头痛（48975 例/550381 例对照）的全基因组关联研究（GWAS）汇总统计数据和 360 个 WM 成像衍生表型（IDP）（31356 个样本），用于测量微观 WM。基于从 GWAS 汇总统计数据中选择的工具变量（IVs），我们进行了双向两样本 MR 分析，以推断偏头痛和微观 WM 之间的双向因果关系。在正向 MR 分析中，我们通过报告 OR 来推断微观 WM 对偏头痛的因果效应，OR 量化了 IDP 每增加 1 个标准差（SD）时偏头痛风险的变化。在反向 MR 分析中，我们通过报告 β 值来推断偏头痛对微观 WM 的因果效应，β 值代表偏头痛引起 IDP 变化的 SD。
结果
三个 WM IDP 与偏头痛有显著的因果关系（p < 3.29 × 10 ，Bonferroni 校正），并通过敏感性分析证明是可靠的。左侧下额枕束模式各向异性（MO）（OR = 1.76，p = 6.46 × 10）和右侧丘脑后辐射方向分散指数（OD）（OR = 0.78，p = 1.86 × 10）的模式对偏头痛有显著的因果作用。偏头痛对左侧小脑上脚 OD 有显著的因果作用（β = -0.09，p = 2.78 × 10）。
结论
我们的研究结果为偏头痛和微观 WM 之间的因果关系提供了遗传证据，为偏头痛的发生和经历提供了对大脑结构的新见解。
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