Causal relationships between migraine and microstructural white matter: a Mendelian randomization study

The Journal of Headache and Pain

Research

Wenhui Zhao¹  Yiheng Tu¹  Lei Zhao¹  Jin Cao² 

[1] 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;School of Life Sciences, Beijing University of Chinese Medicine, Beijing, China;

关键词: Migraine;    Microstructural white matter;    Imaging-derived phenotype;    Causal association;    Mendelian randomization;   

DOI  :  10.1186/s10194-023-01550-z

 received in 2022-12-28, accepted in 2023-02-09,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundMigraine 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).MethodsWe 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.ResultsThree WM IDPs showed significant causal associations (p < 3.29 × 10− 4, 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− 5) and orientation dispersion index (OD) of right posterior thalamic radiation (OR = 0.78, p = 1.86 × 10− 4) 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− 4).ConclusionsOur 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.

【 授权许可】

CC BY   
© The Author(s) 2023

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