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

International Headache Genetics Consortium; HUNT All-in Headache; Danish Blood Donor Study Genomic Cohort; Heidi Hautakangas; Bendik S. Winsvold; Sanni E. Ruotsalainen; Gyda Bjornsdottir; 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 M. Brumpton; Kristoffer Sølvsten Burgdorf; Julie E. Buring; Mona Ameri Chalmer; Irene de Boer; Martin Dichgans; Christian Erikstrup; Markus Färkkilä; Maiken Elvestad Garbrielsen; Mohsen Ghanbari; Knut Hagen; Paavo Häppölä; Jouke Jan Hottenga; Maria G. Hrafnsdottir; Kristian Hveem; Marianne Bakke Johnsen; Mika Kähönen; Espen S. Kristoffersen; Tobias Kurth; Terho Lehtimäki; Lannie Lighart; Sigurdur H. Magnusson; 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; Olafur A. Sveinsson; Thorgeir E. Thorgeirsson; Henrik Ullum; Lisanne S. Vijfhuizen; Thomas Folkmann Hansen

doi:10.1038/s41588-021-00990-0

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

International Headache Genetics Consortium, HUNT All-in Headache, Danish Blood Donor Study Genomic Cohort, Heidi Hautakangas, Bendik S. Winsvold, Sanni E. Ruotsalainen, Gyda Bjornsdottir, 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 M. Brumpton, Kristoffer Sølvsten Burgdorf, Julie E. BuringMona Ameri Chalmer, Irene de Boer, Martin Dichgans, Christian Erikstrup, Markus Färkkilä, Maiken Elvestad Garbrielsen, Mohsen Ghanbari, Knut Hagen, Paavo Häppölä, Jouke Jan Hottenga, Maria G. Hrafnsdottir, Kristian Hveem, Marianne Bakke Johnsen, Mika Kähönen, Espen S. Kristoffersen, Tobias Kurth, Terho Lehtimäki, Lannie Lighart, Sigurdur H. Magnusson, 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, Olafur A. Sveinsson, Thorgeir E. Thorgeirsson, Henrik Ullum, Lisanne S. Vijfhuizen, Thomas Folkmann Hansen

Tutkimustuotos: Artikkeli › Scientific › vertaisarvioitu

Abstrakti

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.

Alkuperäiskieli	Englanti
Sivut	152-160
Sivumäärä	9
Julkaisu	Nature Genetics
Vuosikerta	54
Numero	2
DOI - pysyväislinkit	https://doi.org/10.1038/s41588-021-00990-0
Tila	Julkaistu - helmik. 2022
OKM-julkaisutyyppi	A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä

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!!ASJC Scopus subject areas

Genetics

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10.1038/s41588-021-00990-0Lisenssi: CC BY

s41588-021-00990-0Final published version, 3,81 MBLisenssi: CC BY

https://urn.fi/URN:NBN:fi:tuni-202205195094Lisenssi: CC BY

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International Headache Genetics Consortium, HUNT All-in Headache, Danish Blood Donor Study Genomic Cohort, 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., ... Hansen, T. F. (2022). Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles. Nature Genetics, 54(2), 152-160. https://doi.org/10.1038/s41588-021-00990-0

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

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.",

author = "{International Headache Genetics Consortium} and {HUNT All-in Headache} and {Danish Blood Donor Study Genomic Cohort} and Heidi Hautakangas and Winsvold, {Bendik S.} and Ruotsalainen, {Sanni E.} and Gyda Bjornsdottir and Harder, {Aster V.E.} and Kogelman, {Lisette J.A.} and Thomas, {Laurent F.} and Raymond Noordam and Christian Benner and Padhraig Gormley and Ville Artto and Karina Banasik and Anna Bjornsdottir and Boomsma, {Dorret I.} and Brumpton, {Ben M.} and Burgdorf, {Kristoffer S{\o}lvsten} and Buring, {Julie E.} and Chalmer, {Mona Ameri} and {de Boer}, Irene and Martin Dichgans and Christian Erikstrup and Markus F{\"a}rkkil{\"a} and Garbrielsen, {Maiken Elvestad} and Mohsen Ghanbari and Knut Hagen and Paavo H{\"a}pp{\"o}l{\"a} and Hottenga, {Jouke Jan} and Hrafnsdottir, {Maria G.} and Kristian Hveem and Johnsen, {Marianne Bakke} and Mika K{\"a}h{\"o}nen and Kristoffersen, {Espen S.} and Tobias Kurth and Terho Lehtim{\"a}ki and Lannie Lighart and Magnusson, {Sigurdur H.} and Rainer Malik and Pedersen, {Ole Birger} and Nadine Pelzer and Penninx, {Brenda W.J.H.} and Caroline Ran and Ridker, {Paul M.} and Rosendaal, {Frits R.} and Sigurdardottir, {Gudrun R.} and Skogholt, {Anne Heidi} and Sveinsson, {Olafur A.} and Thorgeirsson, {Thorgeir E.} and Henrik Ullum and Vijfhuizen, {Lisanne S.} and Hansen, {Thomas Folkmann}",

note = "Publisher Copyright: {\textcopyright} 2022. The Author(s).",

year = "2022",

month = feb,

doi = "10.1038/s41588-021-00990-0",

language = "English",

volume = "54",

pages = "152--160",

number = "2",

}

International Headache Genetics Consortium, HUNT All-in Headache, Danish Blood Donor Study Genomic Cohort, Hautakangas, H, Winsvold, BS, Ruotsalainen, SE, Bjornsdottir, G, Harder, AVE, Kogelman, LJA, Thomas, LF, Noordam, R, Benner, C, Gormley, P, Artto, V, Banasik, K, Bjornsdottir, A, Boomsma, DI, Brumpton, BM, Burgdorf, KS, Buring, JE, Chalmer, MA, de Boer, I, Dichgans, M, Erikstrup, C, Färkkilä, M, Garbrielsen, ME, Ghanbari, M, Hagen, K, Häppölä, P, Hottenga, JJ, Hrafnsdottir, MG, Hveem, K, Johnsen, MB, Kähönen, M, Kristoffersen, ES, Kurth, T, Lehtimäki, T, Lighart, L, Magnusson, SH, Malik, R, Pedersen, OB, Pelzer, N, Penninx, BWJH, Ran, C, Ridker, PM, Rosendaal, FR, Sigurdardottir, GR, Skogholt, AH, Sveinsson, OA, Thorgeirsson, TE, Ullum, H, Vijfhuizen, LS & Hansen, TF 2022, 'Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles', Nature Genetics, Vuosikerta 54, Nro 2, Sivut 152-160. https://doi.org/10.1038/s41588-021-00990-0

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 - Hansen, Thomas Folkmann

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.

U2 - 10.1038/s41588-021-00990-0

DO - 10.1038/s41588-021-00990-0

M3 - Article

C2 - 35115687

AN - SCOPUS:85124577579

VL - 54

SP - 152

EP - 160

IS - 2

ER -

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

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