TY - JOUR
T1 - Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles
AU - International Headache Genetics Consortium
AU - HUNT All-in Headache
AU - Danish Blood Donor Study Genomic Cohort
AU - Hautakangas, Heidi
AU - Winsvold, Bendik S.
AU - Ruotsalainen, Sanni E.
AU - Bjornsdottir, Gyda
AU - Harder, Aster V.E.
AU - Kogelman, Lisette J.A.
AU - Thomas, Laurent F.
AU - Noordam, Raymond
AU - Benner, Christian
AU - Gormley, Padhraig
AU - Artto, Ville
AU - Banasik, Karina
AU - Bjornsdottir, Anna
AU - Boomsma, Dorret I.
AU - Brumpton, Ben M.
AU - Burgdorf, Kristoffer Sølvsten
AU - Buring, Julie E.
AU - Chalmer, Mona Ameri
AU - de Boer, Irene
AU - Dichgans, Martin
AU - Erikstrup, Christian
AU - Färkkilä, Markus
AU - Garbrielsen, Maiken Elvestad
AU - Ghanbari, Mohsen
AU - Hagen, Knut
AU - Häppölä, Paavo
AU - Hottenga, Jouke Jan
AU - Hrafnsdottir, Maria G.
AU - Hveem, Kristian
AU - Johnsen, Marianne Bakke
AU - Kähönen, Mika
AU - Kristoffersen, Espen S.
AU - Kurth, Tobias
AU - Lehtimäki, Terho
AU - Lighart, Lannie
AU - Magnusson, Sigurdur H.
AU - Malik, Rainer
AU - Pedersen, Ole Birger
AU - Pelzer, Nadine
AU - Penninx, Brenda W.J.H.
AU - Ran, Caroline
AU - Ridker, Paul M.
AU - Rosendaal, Frits R.
AU - Sigurdardottir, Gudrun R.
AU - Skogholt, Anne Heidi
AU - Sveinsson, Olafur A.
AU - Thorgeirsson, Thorgeir E.
AU - Ullum, Henrik
AU - Vijfhuizen, Lisanne S.
AU - Widén, Elisabeth
N1 - Publisher Copyright:
© 2022, The Author(s).
PY - 2022/2
Y1 - 2022/2
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85124577579
U2 - 10.1038/s41588-021-00990-0
DO - 10.1038/s41588-021-00990-0
M3 - Article
C2 - 35115687
AN - SCOPUS:85124577579
SN - 1061-4036
VL - 54
SP - 152
EP - 160
JO - Nature Genetics
JF - Nature Genetics
IS - 2
ER -