Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes

Autor: Malik, Rainer, Chauhan, Ganesh, Anderson, Christopher D, Salomaa, Veikko, Sapkota, Bishwa R, Schmidt, Reinhold, Schmidt, Carsten O, Schminke, Ulf, Sharma, Pankaj, Slowik, Agnieszka, Sudlow, Cathie L M, Tanislav, Christian, Tatlisumak, Turgut, Chong, Michael, Taylor, Kent D, Thijs, Vincent N S, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Tiedt, Steffen, Trompet, Stella, Tzourio, Christophe, van Duijn, Cornelia M, Walters, Matthew, Wareham, Nicholas J, Adams, Hieab H H, Wassertheil-Smoller, Sylvia, Wilson, James G, Wiggins, Kerri L, Yang, Qiong, Yusuf, Salim, Consortium, AFGen, Epidemiology, Cohorts for Heart and Aging Research in Genomic, Pressure, International Genomics of Blood, Consortium, INVENT, STARNET, Ago, Tetsuro, Bis, Joshua C, Pastinen, Tomi, Ruusalepp, Arno, Schadt, Eric E, Koplev, Simon, Björkegren, Johan L M, Codoni, Veronica, Civelek, Mete, Smith, Nicholas L, Trégouët, David A, Almgren, Peter, Christophersen, Ingrid E, Roselli, Carolina, Lubitz, Steven A, Ellinor, Patrick T, Tai, E Shyong, Kooner, Jaspal S, Kato, Norihiro, He, Jiang, van der Harst, Pim, Elliott, Paul, Amouyel, Philippe, Chambers, John C, Takeuchi, Fumihiko, Johnson, Andrew D, Group, BioBank Japan Cooperative Hospital, Consortium, COMPASS, Consortium, EPIC-CVD, Consortium, EPIC-InterAct, Consortium, International Stroke Genetics, Consortium, METASTROKE, Consortium, Neurology Working Group of the CHARGE, Ay, Hakan, Network, NINDS Stroke Genetics, Study, UK Young Lacunar DNA, Consortium, MEGASTROKE, Sanghera, Dharambir K, Melander, Olle, Jern, Christina, Strbian, Daniel, Fernandez-Cadenas, Israel, Longstreth, W. T., Rolfs, Arndt, Bartz, Traci M, Hata, Jun, Woo, Daniel, Rosand, Jonathan, Pare, Guillaume, Hopewell, Jemma C, Saleheen, Danish, Stefansson, Kari, Worrall, Bradford B, Kittner, Steven J, Seshadri, Sudha, Benavente, Oscar R, Fornage, Myriam, Markus, Hugh S, Howson, Joanna M M, Kamatani, Yoichiro, Debette, Stephanie, Dichgans, Martin, Traylor, Matthew, Sargurupremraj, Muralidharan, Bevan, Steve, Okada, Yukinori, Mishra, Aniket, Rutten-Jacobs, Loes, Giese, Anne-Katrin, van der Laan, Sander W, Gretarsdottir, Solveig, Boncoraglio, Giorgio B, Brown, Robert D, Butterworth, Adam S, Carrera, Caty, Carty, Cara L, Chasman, Daniel I, Chen, Wei-Min, Cole, John W, Correa, Adolfo, Cotlarciuc, Ioana, Cruchaga, Carlos, Danesh, John, de Bakker, Paul I W, DeStefano, Anita L, Hoed, Marcel den, Duan, Qing, Engelter, Stefan T, Falcone, Guido J, Gottesman, Rebecca F, Grewal, Raji P, Gudnason, Vilmundur, Gustafsson, Stefan, Haessler, Jeffrey, Harris, Tamara B, Hassan, Ahamad, Havulinna, Aki S, Heckbert, Susan R, Holliday, Elizabeth G, Howard, George, Hsu, Fang-Chi, Hyacinth, Hyacinth I, Ikram, M Arfan, Ingelsson, Erik, Irvin, Marguerite R, Jian, Xueqiu, Jiménez-Conde, Jordi, Johnson, Julie A, Jukema, J Wouter, Kanai, Masahiro, Keene, Keith L, Kissela, Brett M, Kleindorfer, Dawn O, Kooperberg, Charles, Kubo, Michiaki, Lange, Leslie A, Langefeld, Carl D, Langenberg, Claudia, Launer, Lenore J, Lee, Jin-Moo, Lemmens, Robin, Leys, Didier, Lewis, Cathryn M, Lin, Wei-Yu, Lindgren, Arne G, Lorentzen, Erik, Magnusson, Patrik K, Maguire, Jane, Manichaikul, Ani, McArdle, Patrick F, Meschia, James F, Mitchell, Braxton D, Mosley, Thomas H, Nalls, Michael A, Ninomiya, Toshiharu, O'Donnell, Martin J, Psaty, Bruce M, Pulit, Sara L, Rannikmäe, Kristiina, Reiner, Alexander P, Rexrode, Kathryn M, Rice, Kenneth, Rich, Stephen S, Ridker, Paul M, Rost, Natalia S, Rothwell, Peter M, Rotter, Jerome I, Rundek, Tatjana, Sacco, Ralph L, Sakaue, Saori, Sale, Michele M, Amin, Najaf, Aparicio, Hugo S, Arnett, Donna K, Attia, John, Beiser, Alexa S, Berr, Claudine, Buring, Julie E, Bustamante, Mariana, Caso, Valeria, Cheng, Yu-Ching, Choi, Seung Hoan, Chowhan, Ayesha, Cullell, Natalia, Dartigues, Jean-François, Delavaran, Hossein, Delgado, Pilar, Dörr, Marcus, Engström, Gunnar, Ford, Ian, Gurpreet, Wander S, Hamsten, Anders, Heitsch, Laura, Hozawa, Atsushi, Ibanez, Laura, Ilinca, Andreea, Ingelsson, Martin, Iwasaki, Motoki, Jackson, Rebecca D, Jood, Katarina, den Hoed, Marcel, Jousilahti, Pekka, Kaffashian, Sara, Kalra, Lalit, Kamouchi, Masahiro, Kitazono, Takanari, Kjartansson, Olafur, Kloss, Manja, Koudstaal, Peter J, Krupinski, Jerzy, Labovitz, Daniel L, Laurie, Cathy C, Levi, Christopher R, Li, Linxin, Lind, Lars, Lindgren, Cecilia M, Lioutas, Vasileios, Liu, Yong Mei, Lopez, Oscar L, Makoto, Hirata, Martinez-Majander, Nicolas, Matsuda, Koichi, Minegishi, Naoko, Montaner, Joan, Morris, Andrew P, Muiño, Elena, Müller-Nurasyid, Martina, Norrving, Bo, Ogishima, Soichi, Parati, Eugenio A, Peddareddygari, Leema Reddy, Pedersen, Nancy L, Pera, Joanna, Perola, Markus, Pezzini, Alessandro, Pileggi, Silvana, Rabionet, Raquel, Riba-Llena, Iolanda, Ribasés, Marta, Romero, Jose R, Roquer, Jaume, Rudd, Anthony G, Sarin, Antti-Pekka, Sarju, Ralhan, Sarnowski, Chloe, Sasaki, Makoto, Satizabal, Claudia L, Satoh, Mamoru, Sattar, Naveed, Sawada, Norie, Sibolt, Gerli, Sigurdsson, Ásgeir, Smith, Albert, Sobue, Kenji, Soriano-Tárraga, Carolina, Stanne, Tara, Stine, O Colin, Stott, David J, Strauch, Konstantin, Takai, Takako, Tanaka, Hideo, Tanno, Kozo, Teumer, Alexander, Tomppo, Liisa, Torres-Aguila, Nuria P, Touze, Emmanuel, Tsugane, Shoichiro, Uitterlinden, Andre G, Valdimarsson, Einar M, van der Lee, Sven J, Völzke, Henry, Wakai, Kenji, Weir, David, Williams, Stephen R, Wolfe, Charles D A, Wong, Quenna, Xu, Huichun, Yamaji, Taiki
Přispěvatelé: Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pathology, Epidemiology, Radiology & Nuclear Medicine, Cardiovascular Centre (CVC), Universitat de Barcelona, Traylor, Matthew [0000-0001-6624-8621], Okada, Yukinori [0000-0002-0311-8472], Rutten-Jacobs, Loes [0000-0003-3223-885X], van der Laan, Sander W [0000-0001-6888-1404], Adams, Hieab HH [0000-0003-3687-2508], Almgren, Peter [0000-0002-0473-0241], Amouyel, Philippe [0000-0001-9088-234X], Correa, Adolfo [0000-0002-9501-600X], Cruchaga, Carlos [0000-0002-0276-2899], den Hoed, Marcel [0000-0001-8081-428X], Gustafsson, Stefan [0000-0001-5894-0351], Havulinna, Aki S [0000-0002-4787-8959], Ikram, M Arfan [0000-0003-0372-8585], Jukema, J Wouter [0000-0002-3246-8359], Kanai, Masahiro [0000-0001-5165-4408], Lewis, Cathryn M [0000-0002-8249-8476], Lin, Wei-Yu [0000-0002-9267-7988], Magnusson, Patrik K [0000-0002-7315-7899], Pulit, Sara L [0000-0002-2502-3669], Wiggins, Kerri L [0000-0003-2749-1279], Yang, Qiong [0000-0002-3658-1375], Schadt, Eric E [0000-0002-7892-8808], Koplev, Simon [0000-0002-8586-5614], Civelek, Mete [0000-0002-8141-0284], Trégouët, David A [0000-0001-9084-7800], Christophersen, Ingrid E [0000-0002-6141-4712], Roselli, Carolina [0000-0001-5267-6756], Ellinor, Patrick T [0000-0002-2067-0533], van der Harst, Pim [0000-0002-2713-686X], Elliott, Paul [0000-0002-7511-5684], Takeuchi, Fumihiko [0000-0003-3185-5661], Jern, Christina [0000-0002-7531-2354], Saleheen, Danish [0000-0001-6193-020X], Kamatani, Yoichiro [0000-0001-8748-5597], Dichgans, Martin [0000-0002-0654-387X], Apollo - University of Cambridge Repository
Rok vydání: 2018
Předmět:
Male
0301 basic medicine
COMPASS Consortium
Linkage disequilibrium
Candidate gene
UK Young Lacunar DNA Study
Genome-wide association study
SEPIA
Linkage Disequilibrium
Epigenesis
Genetic
classification [Stroke]
International Stroke Genetics Consortium (ISGC)
0302 clinical medicine
INDEL Mutation
HEMORRHAGIC STROKE
Risk Factors
Pleiotropy
Databases
Genetic
Neurology Working Group of the CHARGE Consortium
WHITE-MATTER HYPERINTENSITIES
Gene Regulatory Networks
Stroke
Genetics & Heredity
Genetics
International Genomics of Blood Pressure (iGEN-BP) Consortium
physiopathology [Stroke]
AFGen Consortium
11 Medical And Health Sciences
Genomics
3. Good health
[MEGASTROKE Consortium]
ISCHEMIC-STROKE
VINTAGE
genetics [Stroke]
CORONARY-ARTERY-DISEASE
Medical genetics
Female
EPIC-InterAct Consortium
MEGASTROKE Consortium
Life Sciences & Biomedicine
Gens
medicine.medical_specialty
SUSCEPTIBILITY LOCI
STARNET
INVENT Consortium
SMALL-VESSEL DISEASE
Biology
Polymorphism
Single Nucleotide
EPIC-CVD Consortium
Article
Chromosomes
HUMAN GENETIC-VARIATION
NINDS Stroke Genetics Network (SiGN)
03 medical and health sciences
ddc:570
Genetic variation
medicine
Humans
Genetic Predisposition to Disease
Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium
Science & Technology
Models
Genetic
COMPLEX TRAITS
Computational Biology
06 Biological Sciences
medicine.disease
METASTROKE Consortium
Human genetics
Cromosomes
BioBank Japan Cooperative Hospital Group
Genòmica
030104 developmental biology
Genes
Genetic Loci
ATRIAL-FIBRILLATION
[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
SUDDEN CARDIAC DEATH
030217 neurology & neurosurgery
Developmental Biology
Genome-Wide Association Study
Zdroj: Nature Genetics
Nat. Genet. 50, 524-537 (2018)
Nature Genetics, Nature Publishing Group, 2018, 50 (4), pp.524-537. ⟨10.1038/s41588-018-0058-3⟩
Nature Genetics, 50(4), 524-+. Nature Publishing Group
NATURE GENETICS
r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
instname
Nature genetics
CORE (RIOXX-UK Aggregator)
Apollo
PubMed Central
Nature Genetics, 50(4), 524-537. Nature Publishing Group
Malik, R, Chauhan, G, Traylor, M, Sargurupremraj, M, Okada, Y, Mishra, A, Rutten-Jacobs, L, Giese, A-K, van der Laan, S W, Gretarsdottir, S, Anderson, C D, Chong, M, Adams, H H H, Ago, T, Almgren, P, Amouyel, P, Ay, H, Bartz, T M, Benavente, O R, Bevan, S, Boncoraglio, G B, Brown Jnr, R D, Butterworth, A S, Carrera, C, Carty, C L, Chasman, D I, Chen, W M, Cole, J W, Correa, A, Cotlarciuc, I, Cruchaga, C, Danesh, J, de Bakker, P IW, DeStefano, A L, den Hoed, M, Duan, Q, Engelter, S T, Falcone, G J, Gottesman, R F, Grewal, R P, Guðnason, V, Gustafsson, S, Haessler, J, Harris, T B, Hassan, A, Havulinna, A S, Heckbert, S R, Holliday, E G, Howard, G, Hsu, F-C, Hyacinth, H I, Arfan Ikram, M, Ingelsson, E, Irvin, M R, Jian, X, Jiménez-Conde, J, Johnson, J A, Jukema, J W, Kanai, M, Keene, K L, Kissela, B M, Kleindorfer, D O, Kooperberg, C, Kubo, M, Lange, L A, Langefeld, C D, Langenberg, C, Launer, L J, Lee, J-M, Lemmens, R, Leys, D, Lewis, C M, Lin, W-Y, Lindgren, A G, Lorentzen, E, Magnusson, P K, Maguire, J, Manichaikul, A, McArdle, P F, Meschia, J F, Mitchell, B D, Mosley, T H, Nalls, M A, Ninomiya, T, O'Donnell, M J, Psaty, B M, Pulit, S L, Rannikmäe, K, Reiner, A P, Rexrode, K M, Rice, K M, Rich, S S, Ridker, P M, Rost, N S, Rothwell, P M, Rotter, J I, Rundek, T, Sacco, R L, Sakaue, S, Sale, M M, Salomaa, V, Sapkota, B R, Schmidt, R, Oliver Schmidt, C, Schminke, U, Sharma, P, Slowik, A, Sudlow, C L M, Tatlisumak, T, Tanislav, C, Taylor, K D, Thijs, V NS, Thorleifsson, G, Thorsteinsdottir, U, Tiedt, S, Trompet, S, Tzourio, C, van Duijn, C M, Walters, M, Wareham, N J, Wassertheil-Smoller, S, Wilson, J G, Wiggins, K L, Yang, Q, Yusuf, S, Bis, J C, Pastinen, T, Ruusalepp, A, Schadt, E E, Koplev, S, Björkegren, J LM, Codoni, V, Civelek, M, Smith, N L, Trégouët, D A, Christophersen, I E, Roselli, C, Lubitz, S A, Ellinor, P T, Shyong Tai, E, Kooner, J S, Kato, N, He, J, van der Harst, P, Elliott, P, Chambers, J C, Takeuchi, F, Johnson, A D, Sanghera, D K, Melander, O, Jern, C, Strbian, D, Fernandez-Cadenas, I, Longstreth Jr, W T, Rolfs, A & Hata, J & Woo, D & Rosand, J & Pare, G & Hopewell, J C & Saleheen, D & Stefansson, K & Worrall, B B & Kittner, S J & Seshadri, S & Fornage, M & Markus, H S & Howson, J M M & Kamatani, Y & Debette, S & Dichgans, M 2018, ' Multi-ancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes ', Nature Genetics, vol. 50, no. 4, pp. 524–537 . https://doi.org/10.1038/s41588-018-0058-3
Recercat. Dipósit de la Recerca de Catalunya
Nature Genetics, 50(4), 524
Nature genetics 50(4), 524-537 (2018). doi:10.1038/s41588-018-0058-3
Dipòsit Digital de la UB
Universidad de Barcelona
r-FSJD: Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
Fundació Sant Joan de Déu
ISSN: 1546-1718
1061-4036
Popis: Stroke has multiple etiologies, but the underlying genes and pathways are largely unknown. We conducted a multiancestry genome-wide-association meta-analysis in 521,612 individuals (67,162 cases and 454,450 controls) and discovered 22 new stroke risk loci, bringing the total to 32. We further found shared genetic variation with related vascular traits, including blood pressure, cardiac traits, and venous thromboembolism, at individual loci (n = 18), and using genetic risk scores and linkage-disequilibrium-score regression. Several loci exhibited distinct association and pleiotropy patterns for etiological stroke sub-types. Eleven new susceptibility loci indicate mechanisms not previously implicated in stroke pathophysiology, with prioritization of risk variants and genes accomplished through bioinformatics analyses using extensive functional datasets. Stroke risk loci were significantly enriched in drug targets for antithrombotic therapy.
Databáze: OpenAIRE
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