Cluster Headache Genomewide Association Study and Meta-Analysis Identifies Eight Loci and Implicates Smoking as Causal Risk Factor
dc.date.accessioned | 2024-02-17T18:07:28Z | |
dc.date.available | 2024-02-17T18:07:28Z | |
dc.date.created | 2023-08-22T13:45:14Z | |
dc.date.issued | 2023 | |
dc.identifier.citation | Winsvold, Bendik Kristoffer Slagsvold Harder, Aster V. E. Ran, Caroline Chalmer, Mona A. Dalmasso, Maria Carolina Ferkingstad, Egil Tripathi, Kumar Parijat Bacchelli, Elena Børte, Sigrid Fourier, Carmen Petersen, Anja S. Vijfhuizen, Lisanne S. Magnusson, Sigurdur H. O'Connor, Emer Bjornsdottir, Gyda Häppölä, Paavo Wang, Yen-Feng Callesen, Ida Kelderman, Tim Gallardo, Victor J de Boer, Irene Olofsgård, Felicia Jennysdotter Heinze, Katja Lund, Nunu Thomas, Laurent Francois Hsu, Chia-Lin Pirinen, Matti Hautakangas, Heidi Ribasés, Marta Guerzoni, Simona Sivakumar, Prasanth Yip, Janice Heinze, Axel Küçükali, Fahri Ostrowski, Sisse R. Pedersen, Ole B. Kristoffersen, Espen Saxhaug Martinsen, Amy Artigas, María S. Lagrata, Susie Cainazzo, Maria Michela Adebimpe, Joycee Quinn, Olivia Göbel, Carl Cirkel, Anna Volk, Alexander E. Heilmann-Heimbach, Stefanie Skogholt, Anne Heidi Gabrielsen, Maiken Elvestad Wilbrink, Leopoldine A. Danno, Daisuke Mehta, Dwij Guðbjartsson, Daníel F. Rosendaal, Frits Richard Willems van Dijk, Ko Fronczek, Rolf Wagner, Michael Scherer, Martin Göbel, Hartmut Sleegers, Kristel Sveinsson, Olafur A. Pani, Luca Zoli, Michele Ramos-Quiroga, Josep A. Dardiotis, Efthimios Steinberg, Anna Riedel-Heller, Steffi Sjöstrand, Christina Thorgeirsson, Thorgeir E. Stefansson, Hreinn Southgate, Laura Trembath, Richard C. Vandrovcova, Jana Noordam, Raymond Paemeleire, Koen Stefansson, Kari Fann, Cathy Shen-Jang Waldenlind, Elisabet Tronvik, Erling Andreas Jensen, Rigmor H. Chen, Shih-Pin Houlden, Henry Terwindt, Gisela M. Kubisch, Christian Maestrini, Elena Vikelis, Michail Pozo-Rosich, Patricia Belin, Andrea C. Matharu, Manjit van den Maagdenberg, Arn M.J.M. Hansen, Thomas Ramirez, Alfredo Zwart, John Anker Henrik . Cluster Headache Genomewide Association Study and Meta-Analysis Identifies Eight Loci and Implicates Smoking as Causal Risk Factor. Annals of Neurology. 2023, 94(4), 713-726 | |
dc.identifier.uri | http://hdl.handle.net/10852/108212 | |
dc.description.abstract | Objective 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. Methods 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. Results 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. Interpretation 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 | |
dc.language | EN | |
dc.rights | Attribution-NonCommercial 4.0 International | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc/4.0/ | |
dc.title | Cluster Headache Genomewide Association Study and Meta-Analysis Identifies Eight Loci and Implicates Smoking as Causal Risk Factor | |
dc.title.alternative | ENEngelskEnglishCluster Headache Genomewide Association Study and Meta-Analysis Identifies Eight Loci and Implicates Smoking as Causal Risk Factor | |
dc.type | Journal article | |
dc.creator.author | Winsvold, Bendik Kristoffer Slagsvold | |
dc.creator.author | Harder, Aster V. E. | |
dc.creator.author | Ran, Caroline | |
dc.creator.author | Chalmer, Mona A. | |
dc.creator.author | Dalmasso, Maria Carolina | |
dc.creator.author | Ferkingstad, Egil | |
dc.creator.author | Tripathi, Kumar Parijat | |
dc.creator.author | Bacchelli, Elena | |
dc.creator.author | Børte, Sigrid | |
dc.creator.author | Fourier, Carmen | |
dc.creator.author | Petersen, Anja S. | |
dc.creator.author | Vijfhuizen, Lisanne S. | |
dc.creator.author | Magnusson, Sigurdur H. | |
dc.creator.author | O'Connor, Emer | |
dc.creator.author | Bjornsdottir, Gyda | |
dc.creator.author | Häppölä, Paavo | |
dc.creator.author | Wang, Yen-Feng | |
dc.creator.author | Callesen, Ida | |
dc.creator.author | Kelderman, Tim | |
dc.creator.author | Gallardo, Victor J | |
dc.creator.author | de Boer, Irene | |
dc.creator.author | Olofsgård, Felicia Jennysdotter | |
dc.creator.author | Heinze, Katja | |
dc.creator.author | Lund, Nunu | |
dc.creator.author | Thomas, Laurent Francois | |
dc.creator.author | Hsu, Chia-Lin | |
dc.creator.author | Pirinen, Matti | |
dc.creator.author | Hautakangas, Heidi | |
dc.creator.author | Ribasés, Marta | |
dc.creator.author | Guerzoni, Simona | |
dc.creator.author | Sivakumar, Prasanth | |
dc.creator.author | Yip, Janice | |
dc.creator.author | Heinze, Axel | |
dc.creator.author | Küçükali, Fahri | |
dc.creator.author | Ostrowski, Sisse R. | |
dc.creator.author | Pedersen, Ole B. | |
dc.creator.author | Kristoffersen, Espen Saxhaug | |
dc.creator.author | Martinsen, Amy | |
dc.creator.author | Artigas, María S. | |
dc.creator.author | Lagrata, Susie | |
dc.creator.author | Cainazzo, Maria Michela | |
dc.creator.author | Adebimpe, Joycee | |
dc.creator.author | Quinn, Olivia | |
dc.creator.author | Göbel, Carl | |
dc.creator.author | Cirkel, Anna | |
dc.creator.author | Volk, Alexander E. | |
dc.creator.author | Heilmann-Heimbach, Stefanie | |
dc.creator.author | Skogholt, Anne Heidi | |
dc.creator.author | Gabrielsen, Maiken Elvestad | |
dc.creator.author | Wilbrink, Leopoldine A. | |
dc.creator.author | Danno, Daisuke | |
dc.creator.author | Mehta, Dwij | |
dc.creator.author | Guðbjartsson, Daníel F. | |
dc.creator.author | Rosendaal, Frits Richard | |
dc.creator.author | Willems van Dijk, Ko | |
dc.creator.author | Fronczek, Rolf | |
dc.creator.author | Wagner, Michael | |
dc.creator.author | Scherer, Martin | |
dc.creator.author | Göbel, Hartmut | |
dc.creator.author | Sleegers, Kristel | |
dc.creator.author | Sveinsson, Olafur A. | |
dc.creator.author | Pani, Luca | |
dc.creator.author | Zoli, Michele | |
dc.creator.author | Ramos-Quiroga, Josep A. | |
dc.creator.author | Dardiotis, Efthimios | |
dc.creator.author | Steinberg, Anna | |
dc.creator.author | Riedel-Heller, Steffi | |
dc.creator.author | Sjöstrand, Christina | |
dc.creator.author | Thorgeirsson, Thorgeir E. | |
dc.creator.author | Stefansson, Hreinn | |
dc.creator.author | Southgate, Laura | |
dc.creator.author | Trembath, Richard C. | |
dc.creator.author | Vandrovcova, Jana | |
dc.creator.author | Noordam, Raymond | |
dc.creator.author | Paemeleire, Koen | |
dc.creator.author | Stefansson, Kari | |
dc.creator.author | Fann, Cathy Shen-Jang | |
dc.creator.author | Waldenlind, Elisabet | |
dc.creator.author | Tronvik, Erling Andreas | |
dc.creator.author | Jensen, Rigmor H. | |
dc.creator.author | Chen, Shih-Pin | |
dc.creator.author | Houlden, Henry | |
dc.creator.author | Terwindt, Gisela M. | |
dc.creator.author | Kubisch, Christian | |
dc.creator.author | Maestrini, Elena | |
dc.creator.author | Vikelis, Michail | |
dc.creator.author | Pozo-Rosich, Patricia | |
dc.creator.author | Belin, Andrea C. | |
dc.creator.author | Matharu, Manjit | |
dc.creator.author | van den Maagdenberg, Arn M.J.M. | |
dc.creator.author | Hansen, Thomas | |
dc.creator.author | Ramirez, Alfredo | |
dc.creator.author | Zwart, John Anker Henrik | |
cristin.unitcode | 185,52,15,0 | |
cristin.unitname | Avdeling for allmennmedisin | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 2 | |
dc.identifier.cristin | 2168764 | |
dc.identifier.bibliographiccitation | info:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Annals of Neurology&rft.volume=94&rft.spage=713&rft.date=2023 | |
dc.identifier.jtitle | Annals of Neurology | |
dc.identifier.volume | 94 | |
dc.identifier.issue | 4 | |
dc.identifier.startpage | 713 | |
dc.identifier.endpage | 726 | |
dc.identifier.doi | https://doi.org/10.1002/ana.26743 | |
dc.type.document | Tidsskriftartikkel | |
dc.type.peerreviewed | Peer reviewed | |
dc.source.issn | 0364-5134 | |
dc.type.version | PublishedVersion | |
dc.relation.project | NFR/328615 |
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