A1 Refereed original research article in a scientific journal
Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles
Authors: Hautakangas Heidi, 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., Burgdorf Kristoffer Sølvsten, 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, International Headache Genetics Consortium, HUNT All-in Headache, Danish Blood Donor Study Genomic Cohort, 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 Matti
Publisher: NATURE PORTFOLIO
Publication year: 2022
Journal: Nature Genetics
Journal name in source: NATURE GENETICS
Journal acronym: NAT GENET
Volume: 54
Issue: 2
First page : 152
Last page: 160
Number of pages: 16
ISSN: 1061-4036
eISSN: 1546-1718
DOI: https://doi.org/10.1038/s41588-021-00990-0
Web address : https://www.nature.com/articles/s41588-021-00990-0
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/174758944
Genome-wide association analyses identify 123 susceptibility loci for migraine and implicate neurovascular mechanisms in its pathophysiology. Subtype analyses highlight risk loci specific for migraine with or without aura in addition to shared risk variants.Migraine 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.
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