dc.contributor | Vall d'Hebron Barcelona Hospital Campus |
dc.contributor.author | Harder, Aster V. E. |
dc.contributor.author | Winsvold, Bendik S. |
dc.contributor.author | Noordam, Raymond |
dc.contributor.author | Vijfhuizen, Lisanne S. |
dc.contributor.author | Børte, Sigrid |
dc.contributor.author | Kogelman, Lisette J. A. |
dc.contributor.author | Pozo Rosich, Patricia |
dc.date.accessioned | 2022-02-03T13:17:36Z |
dc.date.available | 2022-02-03T13:17:36Z |
dc.date.issued | 2021-08 |
dc.identifier.citation | Harder 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.issn | 2079-6382 |
dc.identifier.uri | https://hdl.handle.net/11351/6969 |
dc.description | Headache; Genomewide Association Study |
dc.description.abstract | Objective
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.iso | eng |
dc.publisher | MDPI |
dc.relation.ispartofseries | Annals of neurology;90(2) |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 International |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
dc.source | Scientia |
dc.subject | Cefalàlgia - Aspectes genètics |
dc.subject | Diàtesi |
dc.subject.mesh | Cluster Headache |
dc.subject.mesh | /genetics |
dc.subject.mesh | Genetic Predisposition to Disease |
dc.title | Genetic Susceptibility Loci in Genomewide Association Study of Cluster Headache |
dc.type | info:eu-repo/semantics/article |
dc.identifier.doi | 10.1002/ana.26146 |
dc.subject.decs | cefalea histamínica |
dc.subject.decs | /genética |
dc.subject.decs | predisposición genética a la enfermedad |
dc.relation.publishversion | https://doi.org/10.1002/ana.26146 |
dc.type.version | info:eu-repo/semantics/publishedVersion |
dc.audience | Professionals |
dc.contributor.organismes | Institut 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.pmid | 34180076 |
dc.identifier.wos | 000746540000001 |
dc.rights.accessrights | info:eu-repo/semantics/openAccess |