Genetic Susceptibility Loci in Genomewide Association Study of Cluster Headache
Harder, Aster V. E. (Leiden University Medical Center)
Winsvold, Bendik Slagsvold (Oslo University Hospital (Oslo, Noruega))
Noordam, Raymond (Leiden University Medical Center)
Vijfhuizen, Lisanne S. (Leiden University Medical Center)
Børte, Sigrid (University of Oslo)
Kogelman, Lisette J. A. (Copenhagen University Hospital Rigshospitalet)
de Boer, Irene (Leiden University Medical Center)
Tronvik, Erling (St Olav's University Hospital)
Rosendaal, Frits R. (Leiden University Medical Center)
Willems van Dijk, Ko (Leiden University Medical Center)
O'Connor, Emer (The National Hospital for Neurology and Neurosurgery)
Fourier, Carmen (Karolinska Institutet (Estocolm, Suècia))
Thomas, Laurent F. (St Olav's University Hospital)
Kristoffersen, Espen S. (Akershus University Hospital)
Fronczek, Rolf (Leiden University Medical Center)
Pozo-Rosich, Patricia (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Jensen, Rigmor H. (Copenhagen University Hospital Rigshospitalet)
Ferrari, Michel D.. (Leiden University Medical Center)
Hansen, Thomas F. (Danish Headache Center)
Zwart, John-Anker (University of Oslo)
Terwindt, Gisela M. (Leiden University Medical Center)
van den Maagdenberg, Arn M. J. M. (Leiden University Medical Center)
Universitat Autònoma de Barcelona

Fecha:	2021
Resumen:	Identifying common genetic variants that confer genetic risk for cluster headache. 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. An association was found with cluster headache for 4 independent loci (r 2 < 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 (r 2 = 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. 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.
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Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Publicado en:	Annals of neurology, Vol. 90 (july 2021) , p. 203-216, ISSN 1531-8249

DOI: 10.1002/ana.26146
PMID: 34180076

14 p, 1.9 MB

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