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dc.contributorVall d'Hebron Barcelona Hospital Campus
dc.contributor.authorHarder, Aster V. E.
dc.contributor.authorWinsvold, Bendik S.
dc.contributor.authorNoordam, Raymond
dc.contributor.authorVijfhuizen, Lisanne S.
dc.contributor.authorBørte, Sigrid
dc.contributor.authorKogelman, Lisette J. A.
dc.contributor.authorPozo Rosich, Patricia
dc.date.accessioned2022-02-03T13:17:36Z
dc.date.available2022-02-03T13:17:36Z
dc.date.issued2021-08
dc.identifier.citationHarder AVE, Winsvold BS, Noordam R, Vijfhuizen LS, Børte S, Kogelman LJA, et al. Genetic Susceptibility Loci in Genomewide Association Study of Cluster Headaches. Ann Neurol. 2021 Aug;90(2):203–16.
dc.identifier.issn2079-6382
dc.identifier.urihttp://hdl.handle.net/11351/6969
dc.descriptionHeadache; Genomewide Association Study
dc.description.abstractObjective Identifying common genetic variants that confer genetic risk for cluster headache. Methods We conducted a case–control study in the Dutch Leiden University Cluster headache neuro-Analysis program (LUCA) study population (n = 840) and unselected controls from the Netherlands Epidemiology of Obesity Study (NEO; n = 1,457). Replication was performed in a Norwegian sample of 144 cases from the Trondheim Cluster headache sample and 1,800 controls from the Nord-Trøndelag Health Survey (HUNT). Gene set and tissue enrichment analyses, blood cell-derived RNA-sequencing of genes around the risk loci and linkage disequilibrium score regression were part of the downstream analyses. Results An association was found with cluster headache for 4 independent loci (r2 < 0.1) with genomewide significance (p < 5 × 10−8), rs11579212 (odds ratio [OR] = 1.51, 95% confidence interval [CI] = 1.33–1.72 near RP11-815 M8.1), rs6541998 (OR = 1.53, 95% CI = 1.37–1.74 near MERTK), rs10184573 (OR = 1.43, 95% CI = 1.26–1.61 near AC093590.1), and rs2499799 (OR = 0.62, 95% CI = 0.54–0.73 near UFL1/FHL5), collectively explaining 7.2% of the variance of cluster headache. SNPs rs11579212, rs10184573, and rs976357, as proxy SNP for rs2499799 (r2 = 1.0), replicated in the Norwegian sample (p < 0.05). Gene-based mapping yielded ASZ1 as possible fifth locus. RNA-sequencing indicated differential expression of POLR1B and TMEM87B in cluster headache patients. Interpretation This genomewide association study (GWAS) identified and replicated genetic risk loci for cluster headache with effect sizes larger than those typically seen in complex genetic disorders. ANN NEUROL 2021;90:203–216
dc.language.isoeng
dc.publisherMDPI
dc.relation.ispartofseriesAnnals of neurology;90(2)
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.sourceScientia
dc.subjectCefalàlgia - Aspectes genètics
dc.subjectDiàtesi
dc.subject.meshCluster Headache
dc.subject.mesh/genetics
dc.subject.meshGenetic Predisposition to Disease
dc.titleGenetic Susceptibility Loci in Genomewide Association Study of Cluster Headache
dc.typeinfo:eu-repo/semantics/article
dc.identifier.doi10.1002/ana.26146
dc.subject.decscefalea histamínica
dc.subject.decs/genética
dc.subject.decspredisposición genética a la enfermedad
dc.relation.publishversionhttps://doi.org/10.1002/ana.26146
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.audienceProfessionals
dc.contributor.organismesInstitut Català de la Salut
dc.contributor.authoraffiliation[Harder AVE] Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands. Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands. [Winsvold BS] Department of Research, Innovation and Education, Division of Clinical Neuroscience, Oslo University Hospital, Oslo, Norway. K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway. Department of Neurology, Oslo University Hospital, Oslo, Norway. [Noordam R] Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands. [Vijfhuizen LS] Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands. [Børte S] Department of Research, Innovation and Education, Division of Clinical Neuroscience, Oslo University Hospital, Oslo, Norway. K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway. Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway. [Kogelman LJA] Department of Neurology, Danish Headache Center, Rigshospitalet, Glostrup, Denmark. [Pozo-Rosich P] Grup de Recerca en Cefalea, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Unitat de Cefalea, Servei de Neurologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain
dc.identifier.pmid34180076
dc.identifier.wos000746540000001
dc.rights.accessrightsinfo:eu-repo/semantics/openAccess


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