Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles
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 Solvsten; 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.; Widen, 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.; Stefansson, Hreinn; Stefansson, Kari; van den Maagdenberg, Arn M. J. M.; Hansen, Thomas Folkmann; Ripatti, Samuli; Zwart, John-Anker; Palotie, Aarno; Pirinen, Matti (2022-02-03)
Hautakangas, H., Winsvold, B.S., Ruotsalainen, S.E. et al. Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles. Nat Genet 54, 152–160 (2022). https://doi.org/10.1038/s41588-021-00990-0
© The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
https://creativecommons.org/licenses/by/4.0/
https://urn.fi/URN:NBN:fi-fe2022110764859
Tiivistelmä
Abstract
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.
Kokoelmat
- Avoin saatavuus [31928]