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Get Free AccessMigraine 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.
Heidi Hautakangas, Bendik S. Winsvold, Sanni Ruotsalainen, Gyða Björnsdóttir, Aster V. E. Harder, Lisette J. A. Kogelman, Laurent F. Thomas, Raymond Noordam, Christian Benner, Padhraig Gormley, Ville Artto, Karina Banasik, Anna Bjornsdottir, Dorret I. Boomsma, Ben Brumpton, Kristoffer Sølvsten Burgdorf, Julie E. Buring, Mona Ameri Chalmer, Irene de Boer, Martin Dichgans, Christian Erikstrup, Martti Färkkilâ, Maiken Elvestad Garbrielsen, Mohsen Ghanbari, Knut Hagen, Paavo Häppölä, Jouke‐Jan Hottenga, Maria Gudlaug Hrafnsdottir, Kristian Hveem, Marianne Bakke Johnsen, Mika Kähönen, Espen Saxhaug Kristoffersen, Tobias Kurth, Terho Lehtimäki, Lannie Lighart, Sigurður H. Magnússon, Rainer Malik, Ole Birger Pedersen, Nadine Pelzer, Brenda W.J.H. Penninx, Caroline Ran, Paul M. Ridker, Frits R. Rosendaal, Gudrun R. Sigurdardottir, Anne Heidi Skogholt, Ólafur Sveinsson, Thorgeir E. Thorgeirsson, Henrik Ullum, Lisanne S. Vijfhuizen, Elisabeth Widén, Ko Willems van Dijk, HUNT All-in Headache, Arpo Aromaa, Andrea Carmine Belin, Tobias Freilinger, M. Arfan Ikram, Marjo‐Riitta Järvelin, Olli T. Raitakari, Gisela M. Terwindt, Mikko Kallela, Maija Wessman, Jes Olesen, Daniel I. Chasman, Dale R. Nyholt, Hreinn Stefánsson, Kāri Stefánsson, Arn M. J. M. van den Maagdenberg, Thomas Hansen, Samuli Ripatti, John‐Anker Zwart, Aarno Palotie, Matti Pirinen (2021). Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles. medRxiv (Cold Spring Harbor Laboratory), DOI: 10.1101/2021.01.20.21249647.
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Type
Preprint
Year
2021
Authors
72
Datasets
0
Total Files
0
Language
English
Journal
medRxiv (Cold Spring Harbor Laboratory)
DOI
10.1101/2021.01.20.21249647
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