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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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dc.contributor.author International Headache Genetics Consortium
dc.contributor.author HUNT All-in Headache
dc.contributor.author Danish Blood Donor Study Genomic Cohort
dc.date.accessioned 2022-04-07T01:02:11Z
dc.date.available 2022-04-07T01:02:11Z
dc.date.issued 2022-02-01
dc.identifier.citation 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
dc.identifier.issn 1061-4036
dc.identifier.other 46887295
dc.identifier.other 422bc099-92e0-4953-8829-d0416008242e
dc.identifier.other 85124577579
dc.identifier.other 35115687
dc.identifier.other unpaywall: 10.1038/s41588-021-00990-0
dc.identifier.uri https://hdl.handle.net/20.500.11815/3029
dc.description Funding Information: We thank the study participants for their contribution to this research. We also thank the numerous individuals who contributed to sample collection, storage, handling, phenotyping and genotyping for each of the individual cohorts. We acknowledge the participants and investigators of the FinnGen study. This research has been conducted using the UK Biobank Resource under Application Number 22627. We are supported by following grants: the US National Institute of Neurological Disorders and Stroke (NINDS) of the US National Institutes of Health (NIH) (grant numbers R21NS09296 and R21NS104398 (D.I.C.)), the Finnish innovation fund Sitra and Finska L?kares?llskapet (E.W.), the Academy of Finland (grant nos. 288509, 312076, 336825 (M.P.)), the Sigrid Juselius Foundation (M.P. and S.R.), the Academy of Finland Center of Excellence in Complex Disease Genetics (grant no. 312062 (S.R.)), the Finnish Foundation for Cardiovascular Research (S.R.), University of Helsinki HiLIFE Fellow and Grand Challenge grants (S.R.), The Novo Nordisk Foundation (NNF14CC0001 and NNF17OC0027594 (T.F.H. and K.B.)), CANDY foundation (CEHEAD) (T.F.H.), and the South-Eastern Norway Regional Health Authority (grant no. 2020034 (B.S.W.)). A list of study-specific acknowledgements and funding information can be found in the Supplementary Note. Funding Information: We thank the study participants for their contribution to this research. We also thank the numerous individuals who contributed to sample collection, storage, handling, phenotyping and genotyping for each of the individual cohorts. We acknowledge the participants and investigators of the FinnGen study. This research has been conducted using the UK Biobank Resource under Application Number 22627. We are supported by following grants: the US National Institute of Neurological Disorders and Stroke (NINDS) of the US National Institutes of Health (NIH) (grant numbers R21NS09296 and R21NS104398 (D.I.C.)), the Finnish innovation fund Sitra and Finska Läkaresällskapet (E.W.), the Academy of Finland (grant nos. 288509, 312076, 336825 (M.P.)), the Sigrid Juselius Foundation (M.P. and S.R.), the Academy of Finland Center of Excellence in Complex Disease Genetics (grant no. 312062 (S.R.)), the Finnish Foundation for Cardiovascular Research (S.R.), University of Helsinki HiLIFE Fellow and Grand Challenge grants (S.R.), The Novo Nordisk Foundation (NNF14CC0001 and NNF17OC0027594 (T.F.H. and K.B.)), CANDY foundation (CEHEAD) (T.F.H.), and the South-Eastern Norway Regional Health Authority (grant no. 2020034 (B.S.W.)). A list of study-specific acknowledgements and funding information can be found in the . Publisher Copyright: © 2022, The Author(s).
dc.description.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.
dc.format.extent 9
dc.format.extent 3991334
dc.format.extent 152-160
dc.language.iso en
dc.relation.ispartofseries Nature Genetics; 54(2)
dc.rights info:eu-repo/semantics/openAccess
dc.subject Genarannsóknir
dc.subject Taugasjúkdómafræði
dc.subject Mígreni
dc.subject Gen
dc.subject Krabbameinslæknisfræði
dc.subject Migraine Disorders
dc.subject Genetic Predisposition to Disease
dc.subject Genome-Wide Association Study
dc.subject Humans
dc.subject Migraine Disorders/genetics
dc.subject Molecular Sequence Annotation
dc.subject Genetic Loci
dc.subject Case-Control Studies
dc.subject Central Nervous System/metabolism
dc.subject Migraine with Aura/genetics
dc.subject Alleles
dc.subject Polymorphism, Single Nucleotide
dc.subject Cardiovascular System/metabolism
dc.subject Quantitative Trait Loci
dc.subject Genetics
dc.title Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles
dc.type /dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article
dc.description.version Peer reviewed
dc.identifier.doi 10.1038/s41588-021-00990-0
dc.relation.url http://www.scopus.com/inward/record.url?scp=85124577579&partnerID=8YFLogxK
dc.contributor.department Faculty of Medicine
dc.contributor.department Other departments


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