Cluster Headache Genomewide Association Study and Meta-Analysis Identifies Eight Loci and Implicates Smoking as Causal Risk Factor
Winsvold, Bendik Slagsvold (Oslo University Hospital (Oslo, Noruega))
Harder, Aster (Leiden University Medical Center)
Ran, Caroline (Karolinska Institutet (Estocolm, Suècia))
Chalmer, Mona A. (University of Copenhagen University Hospital)
Dalmasso, Maria Carolina (National University A. Jauretche (UNAJ))
Ferkingstad, Egil (deCODE Genetics (Reykjavík, Islàndia))
Tripathi, Kumar Parijat (Uniklinik Köln (Colònia, Alemanya))
Bacchelli, Elena (Università di Bologna)
Børte, Sigrid (Norwegian University of Science and Technology (NTNU))
Fourier, Carmen (Karolinska Institutet (Estocolm, Suècia))
Petersen, Anja S. (University of Copenhagen University Hospital)
Vijfhuizen, Lisanne S. (Leiden University Medical Center)
Magnusson, Sigurdur H. (deCODE Genetics (Reykjavík, Islàndia))
O'Connor, Emer (University College London)
Bjornsdottir, Gyda (deCODE Genetics (Reykjavík, Islàndia))
Häppölä, Paavo (University of Helsinki)
Wang, Yen-Feng (National Yang Ming Chiao Tung University)
Callesen, Ida (Glostrup University Hospital Copenhagen)
Kelderman, Tim (Universitair Ziekenhuis Gent)
Gallardo López, Victor José (Vall d'Hebron Institut de Recerca (VHIR))
de Boer, Irene (Leiden University Medical Center)
Olofsgård, Felicia Jennysdotter (Karolinska Institutet (Estocolm, Suècia))
Heinze, Katja (Kiel Migraine and Headache Centre)
Lund, Nunu (Glostrup University Hospital Copenhagen)
Thomas, Laurent (Norwegian University of Science and Technology (NTNU))
Hsu, Chia-Lin (Institute of Biomedical Sciences, Academia Sinica)
Pirinen, Matti (University of Helsinki)
Hautakangas, Heidi (University of Helsinki)
Ribasés Haro, Marta (Universitat de Barcelona)
Guerzoni, Simona (Modena University Hospital)
Sivakumar, Prasanth (University College London)
Yip, Janice (University College London)
Heinze, Axel (Kiel Migraine and Headache Centre)
Küçükali, Fahri (University of Antwerp)
Ostrowski, Sisse Rye (University of Copenhagen)
Pedersen, Ole B. (Zealand University Hospital)
Kristoffersen, Espen Saxhaug (Akershus University Hospital)
Martinsen, Amy E. (University of Oslo)
Artigas, María S. (Universitat de Barcelona)
Lagrata, Susie (University College London Queen Square Institute of Neurology and National Hospital for Neurology and Neurosurgery)
Cainazzo, Maria Michela (Modena University Hospital)
Adebimpe, Joycee (University College London)
Quinn, Olivia (University College London)
Göbel, Carl (Universitätsklinikum Schleswig-Holstein)
Cirkel, Anna (Universitätsklinikum Schleswig-Holstein)
Volk, Alexander E. (University Medical Center Hamburg-Eppendorf)
Heilmann-Heimbach, Stefanie (University Hospital Bonn (Bonn, Alemanya))
Skogholt, Anne Heidi (Norwegian University of Science and Technology (NTNU))
Gabrielsen, Maiken E. (Norwegian University of Science and Technology (NTNU))
Wilbrink, Leopoldine A. (Zuyderland Hospital)
Danno, Daisuke (University College London Queen Square Institute of Neurology and National Hospital for Neurology and Neurosurgery)
Mehta, Dwij (University College London Queen Square Institute of Neurology and National Hospital for Neurology and Neurosurgery)
Guðbjartsson, Daníel F. (deCODE Genetics (Reykjavík, Islàndia))
Rosendaal, Frits (Leiden University Medical Center)
Willems van Dijk, Ko (Leiden University Medical Center)
Fronczek, Rolf (Leiden University Medical Center)
Wagner, Michael (University Hospital Bonn (Bonn, Alemanya))
Scherer, Martin (University Medical Center Hamburg-Eppendorf)
Göbel, Hartmut (Kiel Migraine and Headache Centre)
Sleegers, Kristel (University of Antwerp)
Sveinsson, Olafur A. (University of Iceland)
Pani, Luca (University of Miami)
Zoli, Michele (University of Modena and Reggio Emilia)
Ramos-Quiroga, Josep Antoni (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal)
Dardiotis, Efthimios (University of Thessaly)
Steinberg, Anna (Karolinska University Hospital and Karolinska Institutet (Suècia))
Riedel-Heller, Steffi (University of Leipzig)
Sjöstrand, Christina (Danderyd Hospital)
Thorgeirsson, Thorgeir E. (deCODE Genetics (Reykjavík, Islàndia))
Stefánsson, Hreinn (deCODE Genetics (Reykjavík, Islàndia))
Southgate, Laura (King's College London)
Trembath, Richard C. (King's College London)
Vandrovcova, Jana (University College London)
Noordam, Raymond (Leiden University Medical Center)
Paemeleire, Koen (Universitair Ziekenhuis Gent)
Stefánsson, Kári (University of Iceland)
Fann, Cathy Shen-Jang (Institute of Biomedical Sciences, Academia Sinica)
Waldenlind, Elisabet (Karolinska University Hospital and Karolinska Institutet (Suècia))
Tronvik, Erling (Trondheim University Hospital)
Højland Jensen, Rigmor (Copenhagen University Hospital)
Chen, Shih-Pin (Taipei Veterans General Hospital)
Houlden, Henry (University College London)
Terwindt, Gisela (Leiden University Medical Center)
Kubisch, Christian (University Medical Center Hamburg-Eppendorf)
Maestrini, Elena (Università di Bologna)
Vikelis, Michail (Glyfada Headache Center)
Pozo-Rosich, Patricia (Universitat Autònoma de Barcelona. Departament de Medicina)
Belin, Andrea C. (Karolinska Institutet (Estocolm, Suècia))
Matharu, Manjit (University College London Queen Square Institute of Neurology and National Hospital for Neurology and Neurosurgery)
van den Maagdenberg, Arn M. J. M. (Leiden University Medical Center)
Hansen, Thomas F. (University of Copenhagen)
Ramirez, Alfredo (University of Cologne)
Zwart, John-Anker (University of Oslo)

Data:	2023
Resum:	The objective of this study was to aggregate data for the first genomewide association study meta-analysis of cluster headache, to identify genetic risk variants, and gain biological insights. A total of 4,777 cases (3,348 men and 1,429 women) with clinically diagnosed cluster headache were recruited from 10 European and 1 East Asian cohorts. We first performed an inverse-variance genomewide association meta-analysis of 4,043 cases and 21,729 controls of European ancestry. In a secondary trans-ancestry meta-analysis, we included 734 cases and 9,846 controls of East Asian ancestry. Candidate causal genes were prioritized by 5 complementary methods: expression quantitative trait loci, transcriptome-wide association, fine-mapping of causal gene sets, genetically driven DNA methylation, and effects on protein structure. Gene set and tissue enrichment analyses, genetic correlation, genetic risk score analysis, and Mendelian randomization were part of the downstream analyses. The estimated single nucleotide polymorphism (SNP)-based heritability of cluster headache was 14. 5%. We identified 9 independent signals in 7 genomewide significant loci in the primary meta-analysis, and one additional locus in the trans-ethnic meta-analysis. Five of the loci were previously known. The 20 genes prioritized as potentially causal for cluster headache showed enrichment to artery and brain tissue. Cluster headache was genetically correlated with cigarette smoking, risk-taking behavior, attention deficit hyperactivity disorder (ADHD), depression, and musculoskeletal pain. Mendelian randomization analysis indicated a causal effect of cigarette smoking intensity on cluster headache. Three of the identified loci were shared with migraine. This first genomewide association study meta-analysis gives clues to the biological basis of cluster headache and indicates that smoking is a causal risk factor. ANN NEUROL 2023;94:713-726.
Ajuts:	Instituto de Salud Carlos III PI18/01788 Instituto de Salud Carlos III PI19/01224 Instituto de Salud Carlos III PI20/00041 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-01461
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Annals of neurology, Vol. 94 Num. 4 (October 2023) , p. 713-726, ISSN 1531-8249

DOI: 10.1002/ana.26743
PMID: 37486023

14 p, 1.4 MB

El registre apareix a les col·leccions:
Articles > Articles de recerca
Articles > Articles publicats