Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles
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Published:2022-02
Issue:2
Volume:54
Page:152-160
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ISSN:1061-4036
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Container-title:Nature Genetics
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language:en
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Short-container-title:Nat Genet
Author:
Hautakangas HeidiORCID, Winsvold Bendik S.ORCID, Ruotsalainen Sanni E.ORCID, Bjornsdottir Gyda, Harder Aster V. E.ORCID, Kogelman Lisette J. A.ORCID, Thomas Laurent F.ORCID, Noordam RaymondORCID, Benner Christian, Gormley Padhraig, Artto Ville, Banasik KarinaORCID, Bjornsdottir Anna, Boomsma Dorret I.ORCID, Brumpton Ben M.ORCID, Burgdorf Kristoffer Sølvsten, Buring Julie E., Chalmer Mona AmeriORCID, de Boer IreneORCID, Dichgans MartinORCID, Erikstrup ChristianORCID, Färkkilä Markus, Garbrielsen Maiken Elvestad, Ghanbari MohsenORCID, Hagen Knut, Häppölä Paavo, Hottenga Jouke-JanORCID, Hrafnsdottir Maria G., Hveem Kristian, Johnsen Marianne Bakke, Kähönen Mika, Kristoffersen Espen S.ORCID, Kurth TobiasORCID, Lehtimäki TerhoORCID, Lighart LannieORCID, Magnusson Sigurdur H.ORCID, Malik Rainer, Pedersen Ole BirgerORCID, Pelzer NadineORCID, Penninx Brenda W. J. H., Ran CarolineORCID, Ridker Paul M., Rosendaal Frits R., Sigurdardottir Gudrun R., Skogholt Anne HeidiORCID, Sveinsson Olafur A., Thorgeirsson Thorgeir E., Ullum Henrik, Vijfhuizen Lisanne S., Widén Elisabeth, van Dijk Ko WillemsORCID, de Boer Irene, van den Maagdenberg Arn M. J. M., Aromaa Arpo, Belin Andrea CarmineORCID, Freilinger Tobias, Ikram M. ArfanORCID, Järvelin Marjo-RiittaORCID, Raitakari Olli T., Terwindt Gisela M., Kallela Mikko, Wessman Maija, Olesen JesORCID, Chasman Daniel I.ORCID, Nyholt Dale R.ORCID, Stefánsson HreinnORCID, Stefansson KariORCID, van den Maagdenberg Arn M. J. M., Hansen Thomas FolkmannORCID, Ripatti SamuliORCID, Zwart John-AnkerORCID, Palotie AarnoORCID, Pirinen MattiORCID, , ,
Abstract
AbstractMigraine affects over a billion individuals worldwide but its genetic underpinning remains largely unknown. Here, we performed a genome-wide association study of 102,084 migraine cases and 771,257 controls and identified 123 loci, of which 86 are previously unknown. These loci provide an opportunity to evaluate shared and distinct genetic components in the two main migraine subtypes: migraine with aura and migraine without aura. Stratification of the risk loci using 29,679 cases with subtype information indicated three risk variants that seem specific for migraine with aura (in HMOX2, CACNA1A and MPPED2), two that seem specific for migraine without aura (near SPINK2 and near FECH) and nine that increase susceptibility for migraine regardless of subtype. The new risk loci include genes encoding recent migraine-specific drug targets, namely calcitonin gene-related peptide (CALCA/CALCB) and serotonin 1F receptor (HTR1F). Overall, genomic annotations among migraine-associated variants were enriched in both vascular and central nervous system tissue/cell types, supporting unequivocally that neurovascular mechanisms underlie migraine pathophysiology.
Publisher
Springer Science and Business Media LLC
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