Opin vísindi

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

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

Title: Causal relationships between migraine and microstructural white matter : a Mendelian randomization study
Author: International Headache Genetics Consortium (IHGC)
Date: 2023-02-16
Language: English
Scope: 4405466
Department: Faculty of Medicine
Other departments
Series: Journal of Headache and Pain; 24(1)
ISSN: 1129-2369
DOI: 10.1186/s10194-023-01550-z
Subject: Causal association; Imaging-derived phenotype; Mendelian randomization; Microstructural white matter; Migraine; Brain/diagnostic imaging; Genome-Wide Association Study; Humans; Migraine Disorders/diagnostic imaging; Mendelian Randomization Analysis; White Matter/diagnostic imaging; Neurology (clinical); Anesthesiology and Pain Medicine
URI: https://hdl.handle.net/20.500.11815/4449

Show full item record


International Headache Genetics Consortium (IHGC) 2023 , ' Causal relationships between migraine and microstructural white matter : a Mendelian randomization study ' , Journal of Headache and Pain , vol. 24 , no. 1 , 10 , pp. 10 . https://doi.org/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 - 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). 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.


Funding Information: The study was supported by the National Natural Science Foundation of China (32171078), the Scientific Foundation of the Institute of Psychology, Chinese Academy of Sciences (E0CX52, E2CX4015), and Young Elite Scientist Sponsorship Program by the China Association for Science and Technology (E1KX0210). Funding Information: We would like to thank the centre for the Oxford Integrative Neuroimaging (WIN/FMRIB) for the GWAS summary statistics of WM IDPs and the International Headache Genetics Consortium for the GWAS summary statistics of migraine. The members of the International Headache Genetics Consortium (full details are provided in Additional file 1 : Appendix S3): Verneri Anttila, Ville Artto, Andrea C Belin, Anna Bjornsdottir, Gyda Bjornsdottir, Dorret I Boomsma, Sigrid Børte, Mona A Chalmer, Daniel I Chasman, Bru Cormand, Ester Cuenca-Leon, George Davey-Smith, Irene de Boer, Martin Dichgans, Tonu Esko, Tobias Freilinger, Padhraig Gormley, Lyn R Griffiths, Eija Hämäläinen, Thomas F Hansen, Aster VE Harder, Heidi Hautakangas, Marjo Hiekkala, Maria G Hrafnsdottir, M. Arfan Ikram, Marjo-Riitta Järvelin, Risto Kajanne, Mikko Kallela, Jaakko Kaprio, Mari Kaunisto, Lisette JA Kogelman, Espen S Kristoffersen, Christian Kubisch, Mitja Kurki, Tobias Kurth, Lenore Launer, Terho Lehtimäki, Davor Lessel, Lannie Ligthart, Sigurdur H Magnusson, Rainer Malik, Bertram Müller-Myhsok, Carrie Northover, Dale R Nyholt, Jes Olesen, Aarno Palotie, Priit Palta, Linda M Pedersen, Nancy Pedersen, Matti Pirinen, Danielle Posthuma, Patricia Pozo-Rosich, Alice Pressman, Olli Raitakari, Caroline Ran, Gudrun R Sigurdardottir, Hreinn Stefansson, Kari Stefansson, Olafur A Sveinsson, Gisela M Terwindt, Thorgeir E Thorgeirsson, Arn MJM van den Maagdenberg, Cornelia van Duijn, Maija Wessman, Bendik S Winsvold, John-Anker Zwart. Publisher Copyright: © 2023, The Author(s).

Files in this item

This item appears in the following Collection(s)