TY - JOUR
T1 - Causal relationships between migraine and microstructural white matter
T2 - a Mendelian randomization study
AU - Zhao, Lei
AU - Zhao, Wenhui
AU - International Headache Genetics Consortium (IHGC)
AU - Anttila, Verneri
AU - Artto, Ville
AU - Belin, Andrea C.
AU - Bjornsdottir, Anna
AU - Bjornsdottir, Gyda
AU - Boomsma, Dorret I.
AU - Børte, Sigrid
AU - Chalmer, Mona A.
AU - Chasman, Daniel I.
AU - Cormand, Bru
AU - Cuenca-Leon, Ester
AU - Davey-Smith, George
AU - de Boer, Irene
AU - Dichgans, Martin
AU - Esko, Tonu
AU - Freilinger, Tobias
AU - Gormley, Padhraig
AU - Griffiths, Lyn R.
AU - Hämäläinen, Eija
AU - Hansen, Thomas F.
AU - Harder, Aster V. E.
AU - Hautakangas, Heidi
AU - Hiekkala, Marjo
AU - Hrafnsdottir, Maria G.
AU - Ikram, M. Arfan
AU - Järvelin, Marjo-Riitta
AU - Kajanne, Risto
AU - Kallela, Mikko
AU - Kaprio, Jaakko
AU - Kaunisto, Mari
AU - Kogelman, Lisette J. A.
AU - Kristoffersen, Espen S.
AU - Kubisch, Christian
AU - Kurki, Mitja
AU - Kurth, Tobias
AU - Launer, Lenore
AU - Lehtimäki, Terho
AU - Lessel, Davor
AU - Ligthart, Lannie
AU - Magnusson, Sigurdur H.
AU - Malik, Rainer
AU - Müller-Myhsok, Bertram
AU - Northover, Carrie
AU - Nyholt, Dale R.
AU - Olesen, Jes
AU - Palotie, Aarno
AU - Palta, Priit
AU - Posthuma, Danielle
N1 - 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).
PY - 2023/12/1
Y1 - 2023/12/1
N2 - 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.
AB - 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.
KW - Causal association
KW - Imaging-derived phenotype
KW - Mendelian randomization
KW - Microstructural white matter
KW - Migraine
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U2 - https://doi.org/10.1186/s10194-023-01550-z
DO - https://doi.org/10.1186/s10194-023-01550-z
M3 - Article
C2 - 36793015
SN - 1129-2369
VL - 24
JO - Journal of Headache and Pain
JF - Journal of Headache and Pain
IS - 1
M1 - 10
ER -
