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

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 Farkkila; Maiken Elvestad Garbrielsen; Mohsen Ghanbari; Knut Hagen; Paavo Happola; Jouke-Jan Hottenga; Maria G. Hrafnsdottir; Kristian Hveem; Marianne Bakke Johnsen; Mika Kahonen; Espen S. Kristoffersen; Tobias Kurth; Terho Lehtimaki; 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; Elisabeth Widen; Ko Willems van Dijk; Arpo Aromaa; Andrea Carmine Belin; Tobias Freilinger; M. Arfan Ikram; Marjo-Riitta Jarvelin; Olli T. Raitakari; Gisela M. Terwindt; Mikko Kallela; Maija Wessman; Jes Olesen; Daniel, I Chasman; Dale R. Nyholt; Hreinn Stefansson; Kari Stefansson; Arn M. J. M. van den Maagdenberg; Thomas Folkmann Hansen; Samuli Ripatti; John-Anker Zwart; Aarno Palotie; Matti Pirinen

doi:10.1038/s41588-021-00990-0

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

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 DichgansChristian Erikstrup, Markus Farkkila, Maiken Elvestad Garbrielsen, Mohsen Ghanbari, Knut Hagen, Paavo Happola, Jouke-Jan Hottenga, Maria G. Hrafnsdottir, Kristian Hveem, Marianne Bakke Johnsen, Mika Kahonen, Espen S. Kristoffersen, Tobias Kurth, Terho Lehtimaki, 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, Elisabeth Widen, Ko Willems van Dijk, Arpo Aromaa, Andrea Carmine Belin, Tobias Freilinger, M. Arfan Ikram, Marjo-Riitta Jarvelin, Olli T. Raitakari, Gisela M. Terwindt, Mikko Kallela, Maija Wessman, Jes Olesen, Daniel, I Chasman, Dale R. Nyholt, Hreinn Stefansson, Kari Stefansson, Arn M. J. M. van den Maagdenberg, Thomas Folkmann Hansen, Samuli Ripatti, John-Anker Zwart, Aarno Palotie, Matti Pirinen

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

192 Citationer (Scopus)

16 Downloads (Pure)

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.

Originalsprog	Engelsk
Tidsskrift	Nature Genetics
Vol/bind	54
Sider (fra-til)	152-160
Antal sider	16
ISSN	1061-4036
DOI	https://doi.org/10.1038/s41588-021-00990-0
Status	Udgivet - 2022

Adgang til dokumentet

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

FulltextForlagets udgivne version, 3,81 MBLicens: CC BY

Citationsformater

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., ... Pirinen, M. (2022). Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles. Nature Genetics, 54, 152-160. https://doi.org/10.1038/s41588-021-00990-0

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 Sølvsten; Buring, Julie E.; Chalmer, Mona Ameri; de Boer, Irene; Dichgans, Martin; Erikstrup, Christian; Farkkila, Markus; Garbrielsen, Maiken Elvestad; Ghanbari, Mohsen; Hagen, Knut; Happola, Paavo; Hottenga, Jouke-Jan; Hrafnsdottir, Maria G.; Hveem, Kristian; Johnsen, Marianne Bakke; Kahonen, Mika; Kristoffersen, Espen S.; Kurth, Tobias; Lehtimaki, 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; Aromaa, Arpo; Belin, Andrea Carmine; Freilinger, Tobias; Ikram, M. Arfan; Jarvelin, 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.

I: Nature Genetics, Bind 54, 2022, s. 152-160.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

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, Farkkila, M, Garbrielsen, ME, Ghanbari, M, Hagen, K, Happola, P, Hottenga, J-J, Hrafnsdottir, MG, Hveem, K, Johnsen, MB, Kahonen, M, Kristoffersen, ES, Kurth, T, Lehtimaki, 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, Widen, E, van Dijk, KW, Aromaa, A, Belin, AC, Freilinger, T, Ikram, MA, Jarvelin, M-R, Raitakari, OT, Terwindt, GM, Kallela, M, Wessman, M, Olesen, J, Chasman, DI, Nyholt, DR, Stefansson, H, Stefansson, K, van den Maagdenberg, AMJM, Hansen, TF, 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, bind 54, s. 152-160. https://doi.org/10.1038/s41588-021-00990-0

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 Sølvsten ; Buring, Julie E. ; Chalmer, Mona Ameri ; de Boer, Irene ; Dichgans, Martin ; Erikstrup, Christian ; Farkkila, Markus ; Garbrielsen, Maiken Elvestad ; Ghanbari, Mohsen ; Hagen, Knut ; Happola, Paavo ; Hottenga, Jouke-Jan ; Hrafnsdottir, Maria G. ; Hveem, Kristian ; Johnsen, Marianne Bakke ; Kahonen, Mika ; Kristoffersen, Espen S. ; Kurth, Tobias ; Lehtimaki, 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 ; Aromaa, Arpo ; Belin, Andrea Carmine ; Freilinger, Tobias ; Ikram, M. Arfan ; Jarvelin, 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. / Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles. I: Nature Genetics. 2022 ; Bind 54. s. 152-160.

@article{44fdc070b0ce4d5099f63710caabc707,

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 = "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 Farkkila and Garbrielsen, {Maiken Elvestad} and Mohsen Ghanbari and Knut Hagen and Paavo Happola and Jouke-Jan Hottenga and Hrafnsdottir, {Maria G.} and Kristian Hveem and Johnsen, {Marianne Bakke} and Mika Kahonen and Kristoffersen, {Espen S.} and Tobias Kurth and Terho Lehtimaki 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 Elisabeth Widen and {van Dijk}, {Ko Willems} and Arpo Aromaa and Belin, {Andrea Carmine} and Tobias Freilinger and Ikram, {M. Arfan} and Marjo-Riitta Jarvelin and Raitakari, {Olli T.} and Terwindt, {Gisela M.} and Mikko Kallela and Maija Wessman and Jes Olesen and Chasman, {Daniel, I} and Nyholt, {Dale R.} and Hreinn Stefansson and Kari Stefansson and {van den Maagdenberg}, {Arn M. J. M.} and Hansen, {Thomas Folkmann} and Samuli Ripatti and John-Anker Zwart and Aarno Palotie and Matti Pirinen",

year = "2022",

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

language = "English",

volume = "54",

pages = "152--160",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "nature publishing group",

}

TY - JOUR

T1 - Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles

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 - Farkkila, Markus

AU - Garbrielsen, Maiken Elvestad

AU - Ghanbari, Mohsen

AU - Hagen, Knut

AU - Happola, Paavo

AU - Hottenga, Jouke-Jan

AU - Hrafnsdottir, Maria G.

AU - Hveem, Kristian

AU - Johnsen, Marianne Bakke

AU - Kahonen, Mika

AU - Kristoffersen, Espen S.

AU - Kurth, Tobias

AU - Lehtimaki, 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 - Widen, Elisabeth

AU - van Dijk, Ko Willems

AU - Aromaa, Arpo

AU - Belin, Andrea Carmine

AU - Freilinger, Tobias

AU - Ikram, M. Arfan

AU - Jarvelin, Marjo-Riitta

AU - Raitakari, Olli T.

AU - Terwindt, Gisela M.

AU - Kallela, Mikko

AU - Wessman, Maija

AU - Olesen, Jes

AU - Chasman, Daniel, I

AU - Nyholt, Dale R.

AU - Stefansson, Hreinn

AU - Stefansson, Kari

AU - van den Maagdenberg, Arn M. J. M.

AU - Hansen, Thomas Folkmann

AU - Ripatti, Samuli

AU - Zwart, John-Anker

AU - Palotie, Aarno

AU - Pirinen, Matti

PY - 2022

Y1 - 2022

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 - Journal article

C2 - 35115687

VL - 54

SP - 152

EP - 160

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

ER -