HMG-CoA reductase is a potential therapeutic target for migraine: a mendelian randomization study

Kang Qu, Ming Xi Li, Peng Yu, Bai Hua Wu, Miao Shi, Ming Dong, Aarno Palotie, Alice Pressman, Andrea C. Belin, Anna Bjornsdottir, Arn M.J.M. van den Maagdenberg, Aster V.E. Harder, Bendik S. Winsvold, Bertram Müller-Myhsok, Bru Cormand, Caroline Ran, Carrie Northover, Christian Kubisch, Cornelia van Duijn, Dale R. NyholtDaniel I. Chasman, Danielle Posthuma, Davor Lessel, Dorret I. Boomsma, Eija Hämäläinen, Espen S. Kristoffersen, Ester Cuenca-Leon, George Davey-Smith, Gisela M. Terwindt, Gudrun R. Sigurdardottir, Gyda Bjornsdottir, Heidi Hautakangas, Hreinn Stefansson, Irene de Boer, Jaakko Kaprio, Jes Olesen, John Anker Zwart, Kari Stefansson, Lannie Ligthart, Lenore Launer, Linda M. Pedersen, Lisette J.A. Kogelman, Lyn R. Griffiths, M. Arfan Ikram, Maija Wessman, Mari Kaunisto, Maria G. Hrafnsdottir, Marjo Hiekkala, Marjo Riitta Järvelin, Martin Dichgans, Matti Pirinen, Mikko Kallela, Mitja Kurki, Mona A. Chalmer, Nancy Pedersen, Olafur A. Sveinsson, Olli Raitakari, Padhraig Gormley, Patricia Pozo-Rosich, Priit Palta, Rainer Malik, Risto Kajanne, Sigrid Børte, Sigurdur H. Magnusson, Terho Lehtimäki, Thomas F. Hansen, Thorgeir E. Thorgeirsson, Tobias Freilinger, Tobias Kurth, Tonu Esko, Verneri Anttila, Ville Artto

    Research output: Contribution to journalArticleAcademicpeer-review

    Abstract

    Statins are thought to have positive effects on migraine but existing data are inconclusive. We aimed to evaluate the causal effect of such drugs on migraines using Mendelian randomization. We used four types of genetic instruments as proxies for HMG-CoA reductase inhibition. We included the expression quantitative trait loci of the HMG-CoA reductase gene and genetic variation within or near the HMG-CoA reductase gene region. Variants were associated with low-density lipoprotein cholesterol, apolipoprotein B, and total cholesterol. Genome-wide association study summary data for the three lipids were obtained from the UK Biobank. Comparable data for migraine were obtained from the International Headache Genetic Consortium and the FinnGen Consortium. Inverse variance weighting method was used for the primary analysis. Additional analyses included pleiotropic robust methods, colocalization, and meta-analysis. Genetically determined high expression of HMG-CoA reductase was associated with an increased risk of migraines (OR = 1.55, 95% CI 1.30–1.84, P = 6.87 × 10−7). Similarly, three genetically determined HMG-CoA reductase-mediated lipids were associated with an increased risk of migraine. These conclusions were consistent across meta-analyses. We found no evidence of bias caused by pleiotropy or genetic confounding factors. These findings support the hypothesis that statins can be used to treat migraine.

    Original languageEnglish
    Article number12094
    Pages (from-to)1-11
    Number of pages11
    JournalScientific reports
    Volume14
    Early online date27 May 2024
    DOIs
    Publication statusPublished - 2024

    Keywords

    • HMG-CoA reductase
    • Mendelian randomization
    • Migraine
    • Statins

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