Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles
Author:
Hautakangas HeidiORCID, Winsvold Bendik S., Ruotsalainen Sanni E., Bjornsdottir Gyda, Harder Aster V. E., Kogelman Lisette J. A., Thomas Laurent F., Noordam Raymond, Benner Christian, Gormley Padhraig, Artto Ville, Banasik Karina, Bjornsdottir Anna, Boomsma Dorret I., Brumpton Ben M., Sølvsten Burgdorf Kristoffer, Buring Julie E., Chalmer Mona Ameri, de Boer Irene, Dichgans Martin, Erikstrup Christian, Färkkilä Markus, Garbrielsen Maiken Elvestad, Ghanbari Mohsen, Hagen Knut, Häppölä Paavo, Hottenga Jouke-Jan, Hrafnsdottir Maria G., Hveem Kristian, Johnsen Marianne Bakke, Kähönen Mika, Kristoffersen Espen S., Kurth Tobias, Lehtimäki Terho, Lighart Lannie, Magnusson Sigurdur H., Malik Rainer, Pedersen Ole Birger, Pelzer Nadine, Penninx Brenda W. J. H., Ran Caroline, Ridker Paul M., Rosendaal Frits R., Sigurdardottir Gudrun R., Skogholt Anne Heidi, Sveinsson Olafur A., Thorgeirsson Thorgeir E., Ullum Henrik, Vijfhuizen Lisanne S., Widén Elisabeth, van Dijk Ko Willems, Headache HUNT All-in, Aromaa Arpo, Belin Andrea Carmine, Freilinger Tobias, Ikram M. Arfan, Järvelin Marjo-Riitta, Raitakari Olli T., Terwindt Gisela M., Kallela Mikko, Wessman Maija, Olesen Jes, Chasman Daniel I., Nyholt Dale R., Stefánsson Hreinn, Stefansson Kari, van den Maagdenberg Arn M. J. M., Hansen Thomas Folkmann, Ripatti Samuli, Zwart John-Anker, Palotie Aarno, Pirinen MattiORCID, ,
Abstract
AbstractMigraine affects over a billion individuals worldwide but its genetic underpinning remains largely unknown. This genome-wide association study (GWAS) of 102,084 migraine cases and 771,257 controls identified 123 loci of which 86 are novel. The loci provide an opportunity to evaluate shared and distinct genetic components in the two main migraine subtypes: migraine with aura and migraine without aura. A stratification of the risk loci using 29,679 cases with subtype information, of which approximately half have never been used in a GWAS before, indicated three risk variants that appear specific for migraine with aura (in HMOX2, CACNA1A and MPPED2), two that appear 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
Cold Spring Harbor Laboratory
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