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Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles

Authors :
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.
Burgdorf, K.S.
Buring, J.E.
Chalmer, M.A.
Boer, I. de
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.
Dijk, K.W. van
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.
Maagdenberg, A.M.J.M. van den
Hansen, T.F.
Ripatti, S.
Zwart, J.A.
Palotie, A.
Pirinen, M.
Int Headache Genetics Consortium
HUNT All-in Headache
Danish Blood Donor Study Genomic C
Biological Psychology
APH - Mental Health
APH - Methodology
APH - Health Behaviors & Chronic Diseases
APH - Personalized Medicine
Sociology and Social Gerontology
Institute for Molecular Medicine Finland
Statistical and population genetics
Complex Disease Genetics
Clinicum
HUS Helsinki and Uusimaa Hospital District
HUS Neurocenter
Neurologian yksikkö
Genomics of Neurological and Neuropsychiatric Disorders
Centre of Excellence in Complex Disease Genetics
Genomic Discoveries and Clinical Translation
Biosciences
Faculty Common Matters (Faculty of Social Sciences)
Department of Public Health
Biostatistics Helsinki
Research Programs Unit
Research Programme of Molecular Medicine
Department of Mathematics and Statistics
Helsinki Institute for Information Technology
Tampere University
Department of Clinical Physiology and Nuclear Medicine
Clinical Medicine
Department of Clinical Chemistry
Epidemiology
Psychiatry
Amsterdam Neuroscience - Complex Trait Genetics
Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep
APH - Digital Health
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.

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