Genome-Wide Association Study Identifies Risk Loci for Cluster Headache.
Journal
Annals of neurology
ISSN: 1531-8249
Titre abrégé: Ann Neurol
Pays: United States
ID NLM: 7707449
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
revised:
26
06
2021
received:
25
09
2020
accepted:
28
06
2021
pubmed:
30
6
2021
medline:
9
11
2021
entrez:
29
6
2021
Statut:
ppublish
Résumé
This study was undertaken to identify susceptibility loci for cluster headache and obtain insights into relevant disease pathways. We carried out a genome-wide association study, where 852 UK and 591 Swedish cluster headache cases were compared with 5,614 and 1,134 controls, respectively. Following quality control and imputation, single variant association testing was conducted using a logistic mixed model for each cohort. The 2 cohorts were subsequently combined in a merged analysis. Downstream analyses, such as gene-set enrichment, functional variant annotation, prediction and pathway analyses, were performed. Initial independent analysis identified 2 replicable cluster headache susceptibility loci on chromosome 2. A merged analysis identified an additional locus on chromosome 1 and confirmed a locus significant in the UK analysis on chromosome 6, which overlaps with a previously known migraine locus. The lead single nucleotide polymorphisms were rs113658130 (p = 1.92 × 10 We identified and replicated several genome-wide significant associations supporting a genetic predisposition in cluster headache in a genome-wide association study involving 1,443 cases. Replication in larger independent cohorts combined with comprehensive phenotyping, in relation to, for example, treatment response and cluster headache subtypes, could provide unprecedented insights into genotype-phenotype correlations and the pathophysiological pathways underlying cluster headache. ANN NEUROL 2021;90:193-202.
Types de publication
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
193-202Subventions
Organisme : Brain Research UK
Organisme : Health education England
Organisme : Hjärnfonden
ID : FO2018-0008
Organisme : Karolinska Institutet Research Funds
ID : 2018-01738
Organisme : Vetenskapsrådet
ID : 2017-01096
Organisme : Wellcome Trust and strategic award
ID : WT093205 MA
Organisme : Wellcome Trust and strategic award
ID : WT104033AIA
Organisme : Wellcome Trust Institutional Strategic Support Fund
ID : 204809/Z/16/Z
Organisme : University of London
Organisme : Brain Foundation
Organisme : Swedish Research Council
Organisme : Medical Research Council
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2021 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
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