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 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; Jes Olesen; Thomas Folkmann Hansen; International Headache Genetics Consortium

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 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, Jes Olesen, Thomas Folkmann Hansen, International Headache Genetics Consortium

266 Citationer (Scopus)

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
Udgave nummer	2
Sider (fra-til)	152-160
Antal sider	9
ISSN	1061-4036
DOI	https://doi.org/10.1038/s41588-021-00990-0
Status	Udgivet - 2022

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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., ... International Headache Genetics Consortium (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

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, J-J, 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, Olesen, J , Hansen, TF & International Headache Genetics Consortium 2022, 'Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles', Nature Genetics, bind 54, nr. 2, s. 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 = "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 Jouke-Jan Hottenga 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 Jes Olesen and Hansen, {Thomas Folkmann} and {International Headache Genetics Consortium}",

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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 - 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 - Olesen, Jes

AU - Hansen, Thomas Folkmann

AU - International Headache Genetics Consortium

PY - 2022

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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.

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

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