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Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles
- Source :
- Nature genetics, 54(2), 152-160. Nature Publishing Group, Nature Genetics, International Headache Genetics Consortium, HUNT All-in Headache & Danish Blood Donor Study Genomic Cohort 2022, ' Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles ', Nature Genetics, vol. 54, no. 2, pp. 152-160 . https://doi.org/10.1038/s41588-021-00990-0, Nature Genetics, 54, 152-160. NATURE PORTFOLIO, Hautakangas, H, Winsvold, B S, Ruotsalainen, S E, Bjornsdottir, G, Harder, A V E, Kogelman, L J A, Thomas, L F, Noordam, R, Benner, C, Gormley, P, Artto, V, Banasik, K, Bjornsdottir, A, Boomsma, D I, Brumpton, B M, Burgdorf, K S, Buring, J E, Chalmer, M A, de Boer, I, Dichgans, M, Erikstrup, C, Farkkila, M, Garbrielsen, M E, Ghanbari, M, Hagen, K, Happola, P, Hottenga, J-J, Hrafnsdottir, M G, Hveem, K, Johnsen, M B, Kahonen, M, Kristoffersen, E S, Kurth, T, Lehtimaki, T, Lighart, L, Magnusson, S H, Malik, R, Pedersen, O B, Pelzer, N, Penninx, B W J H, Ran, C, Ridker, P M, Rosendaal, F R, Sigurdardottir, G R, Skogholt, A H, Sveinsson, O A, Thorgeirsson, T E, Ullum, H, Vijfhuizen, L S, Widen, E, van Dijk, K W, Aromaa, A, Belin, A C, Freilinger, T, Ikram, M A, Jarvelin, M-R, Raitakari, O T, Terwindt, G M, Kallela, M, Wessman, M, Olesen, J, Chasman, D I, Nyholt, D R, Stefansson, H, Stefansson, K, van den Maagdenberg, A M J M, Hansen, T F, Ripatti, S, Zwart, J-A, Palotie, A & Pirinen, M 2022, ' Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles ', Nature Genetics, vol. 54, pp. 152-160 . https://doi.org/10.1038/s41588-021-00990-0, Hautakangas, H, Winsvold, B S, Ruotsalainen, S E, Bjornsdottir, G, Harder, A V E, Kogelman, L J A, Thomas, L F, Noordam, R, Benner, C, Gormley, P, Artto, V, Banasik, K, Bjornsdottir, A, Boomsma, D I, Brumpton, B M, Burgdorf, K S, Buring, J E, Chalmer, M A, de Boer, I, Dichgans, M, Erikstrup, C, Färkkilä, M, Garbrielsen, M E, Ghanbari, M, Hagen, K, Häppölä, P, Hottenga, J J, Hrafnsdottir, M G, Hveem, K, Johnsen, M B, Kähönen, M, Kristoffersen, E S, Kurth, T, Lehtimäki, T, Lighart, L, Magnusson, S H, Malik, R, Pedersen, O B, Pelzer, N, Penninx, B W J H, Ran, C, Ridker, P M, Rosendaal, F R, Sigurdardottir, G R, Skogholt, A H, Sveinsson, O A, Thorgeirsson, T E, Ullum, H, Vijfhuizen, L S, Widen, E, van Dijk, K W, International Headache Genetics Consortium, HUNT All-in Headache, Danish Blood Donor Study Genomic Cohort, Aromaa, A, Belin, A C, Freilinger, T, Ikram, M A, Järvelin, M-R, Raitakari, O T, Terwindt, G M, Kallela, M, Wessman, M, Olesen, J, Chasman, D I, Nyholt, D R, Stefansson, H, Stefansson, K, van den Maagdenberg, A M J M, Hansen, T F, Ripatti, S, Zwart, J-A, Palotie, A & Pirinen, M 2022, ' Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles ', Nature Genetics, vol. 54, no. 2, pp. 152-160 . https://doi.org/10.1038/s41588-021-00990-0, Nature Genetics, 54(2), 152-160. Nature Publishing Group, Hautakangas, H, Winsvold, B S, Boomsma, D I, Hottenga, J-J, Ligthart, L, Penninx, B W J H, Palotie, A, Pirinen, M & International Headache Genetics Consortium 2022, ' Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles ', Nature genetics, vol. 54, no. 2, pp. 152-160 . https://doi.org/10.1038/s41588-021-00990-0
- Publication Year :
- 2022
-
Abstract
- 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.
- Subjects :
- Central Nervous System
SUSCEPTIBILITY LOCI
Migraine Disorders
Migraine with Aura
Quantitative Trait Loci
PATHOPHYSIOLOGY
Genome-wide association studies
Cardiovascular System
Polymorphism, Single Nucleotide
Genetics
Humans
Genetic Predisposition to Disease
TRANSCRIPTOME
AURA
Migraine
Alleles
METAANALYSIS
GENE-EXPRESSION
ARCHITECTURE
MUTATIONS
HERITABILITY
1184 Genetics, developmental biology, physiology
Molecular Sequence Annotation
ASSOCIATION
3142 Public health care science, environmental and occupational health
Genetic Loci
Case-Control Studies
3111 Biomedicine
Genome-Wide Association Study
Subjects
Details
- Language :
- English
- ISSN :
- 10614036
- Database :
- OpenAIRE
- Journal :
- Nature genetics, 54(2), 152-160. Nature Publishing Group, Nature Genetics, International Headache Genetics Consortium, HUNT All-in Headache & Danish Blood Donor Study Genomic Cohort 2022, ' Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles ', Nature Genetics, vol. 54, no. 2, pp. 152-160 . https://doi.org/10.1038/s41588-021-00990-0, Nature Genetics, 54, 152-160. NATURE PORTFOLIO, Hautakangas, H, Winsvold, B S, Ruotsalainen, S E, Bjornsdottir, G, Harder, A V E, Kogelman, L J A, Thomas, L F, Noordam, R, Benner, C, Gormley, P, Artto, V, Banasik, K, Bjornsdottir, A, Boomsma, D I, Brumpton, B M, Burgdorf, K S, Buring, J E, Chalmer, M A, de Boer, I, Dichgans, M, Erikstrup, C, Farkkila, M, Garbrielsen, M E, Ghanbari, M, Hagen, K, Happola, P, Hottenga, J-J, Hrafnsdottir, M G, Hveem, K, Johnsen, M B, Kahonen, M, Kristoffersen, E S, Kurth, T, Lehtimaki, T, Lighart, L, Magnusson, S H, Malik, R, Pedersen, O B, Pelzer, N, Penninx, B W J H, Ran, C, Ridker, P M, Rosendaal, F R, Sigurdardottir, G R, Skogholt, A H, Sveinsson, O A, Thorgeirsson, T E, Ullum, H, Vijfhuizen, L S, Widen, E, van Dijk, K W, Aromaa, A, Belin, A C, Freilinger, T, Ikram, M A, Jarvelin, M-R, Raitakari, O T, Terwindt, G M, Kallela, M, Wessman, M, Olesen, J, Chasman, D I, Nyholt, D R, Stefansson, H, Stefansson, K, van den Maagdenberg, A M J M, Hansen, T F, Ripatti, S, Zwart, J-A, Palotie, A & Pirinen, M 2022, ' Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles ', Nature Genetics, vol. 54, pp. 152-160 . https://doi.org/10.1038/s41588-021-00990-0, Hautakangas, H, Winsvold, B S, Ruotsalainen, S E, Bjornsdottir, G, Harder, A V E, Kogelman, L J A, Thomas, L F, Noordam, R, Benner, C, Gormley, P, Artto, V, Banasik, K, Bjornsdottir, A, Boomsma, D I, Brumpton, B M, Burgdorf, K S, Buring, J E, Chalmer, M A, de Boer, I, Dichgans, M, Erikstrup, C, Färkkilä, M, Garbrielsen, M E, Ghanbari, M, Hagen, K, Häppölä, P, Hottenga, J J, Hrafnsdottir, M G, Hveem, K, Johnsen, M B, Kähönen, M, Kristoffersen, E S, Kurth, T, Lehtimäki, T, Lighart, L, Magnusson, S H, Malik, R, Pedersen, O B, Pelzer, N, Penninx, B W J H, Ran, C, Ridker, P M, Rosendaal, F R, Sigurdardottir, G R, Skogholt, A H, Sveinsson, O A, Thorgeirsson, T E, Ullum, H, Vijfhuizen, L S, Widen, E, van Dijk, K W, International Headache Genetics Consortium, HUNT All-in Headache, Danish Blood Donor Study Genomic Cohort, Aromaa, A, Belin, A C, Freilinger, T, Ikram, M A, Järvelin, M-R, Raitakari, O T, Terwindt, G M, Kallela, M, Wessman, M, Olesen, J, Chasman, D I, Nyholt, D R, Stefansson, H, Stefansson, K, van den Maagdenberg, A M J M, Hansen, T F, Ripatti, S, Zwart, J-A, Palotie, A & Pirinen, M 2022, ' Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles ', Nature Genetics, vol. 54, no. 2, pp. 152-160 . https://doi.org/10.1038/s41588-021-00990-0, Nature Genetics, 54(2), 152-160. Nature Publishing Group, Hautakangas, H, Winsvold, B S, Boomsma, D I, Hottenga, J-J, Ligthart, L, Penninx, B W J H, Palotie, A, Pirinen, M & International Headache Genetics Consortium 2022, ' Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles ', Nature genetics, vol. 54, no. 2, pp. 152-160 . https://doi.org/10.1038/s41588-021-00990-0
- Accession number :
- edsair.doi.dedup.....271e89f31a913a67875ee7088a9a1e7c
- Full Text :
- https://doi.org/10.1038/s41588-021-00990-0