Contribution of Common Genetic Variants to Risk of Early-Onset Ischemic Stroke
Background and objectives: Current genome-wide association studies of ischemic stroke have focused primarily on late-onset disease. As a complement to these studies, we sought to identify the contribution of common genetic variants to risk of early-onset ischemic stroke. Methods: We performed a meta...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2022 |
| País: | España |
| Institución: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repositorio: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:2445/219351 |
| Acceso en línea: | https://hdl.handle.net/2445/219351 |
| Access Level: | acceso abierto |
| Palabra clave: | Isquèmia cerebral Genètica Embòlia i trombosi cerebral Cerebral ischemia Genetics Cerebral embolism and thrombosis |
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España |
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| dc.title.none.fl_str_mv |
Contribution of Common Genetic Variants to Risk of Early-Onset Ischemic Stroke |
| title |
Contribution of Common Genetic Variants to Risk of Early-Onset Ischemic Stroke |
| spellingShingle |
Contribution of Common Genetic Variants to Risk of Early-Onset Ischemic Stroke Jaworek, Thomas Isquèmia cerebral Genètica Embòlia i trombosi cerebral Cerebral ischemia Genetics Cerebral embolism and thrombosis |
| title_short |
Contribution of Common Genetic Variants to Risk of Early-Onset Ischemic Stroke |
| title_full |
Contribution of Common Genetic Variants to Risk of Early-Onset Ischemic Stroke |
| title_fullStr |
Contribution of Common Genetic Variants to Risk of Early-Onset Ischemic Stroke |
| title_full_unstemmed |
Contribution of Common Genetic Variants to Risk of Early-Onset Ischemic Stroke |
| title_sort |
Contribution of Common Genetic Variants to Risk of Early-Onset Ischemic Stroke |
| dc.creator.none.fl_str_mv |
Jaworek, Thomas Xu, Huichun Gaynor, Brady J. Cole, John W. Rannikmae, Kristiina Stanne, Tara M. Tomppo, Liisa Abedi, Vida Amouyel, Philippe Armstrong, Nicole D. Attia, John Bell, Steven Benavente, Oscar R. Boncoraglio, Giorgio B. Butterworth, Adam Carcel-Marquez, Jara Chen, Zhengming Chong, Michael Cruchaga, Carlos Cushman, Mary Danesh, John Debette, Stéphanie Duggan, David J. Durda, Jon Peter Engstrom, Gunnar Enzinger, Chris Faul, Jessica D. Fecteau, Natalie S. Fernandez-Cadenas, Israel Gieger, Christian Giese, Anne-Katrin Grewal, Raji P. Grittner, Ulrike Havulinna, Aki S. Heitsch, Laura Hochberg, Marc C. Holliday, Elizabeth Hu, Jie Ilinca, Andreea Irvin, Marguerite R. Jackson, Rebecca D. Jacob, Mina A. Rabionet Janssen, Raquel Jiménez Conde, Jordi Johnson, Julie A. Kamatani, Yoichiro Kardia, Sharon L. R. Koido, Masaru Kubo, Michiaki Lange, Leslie Lee, Jin-Moo Lemmens, Robin Levi, Christopher R. Li, Jiang Li, Liming Lin, Kuang Lopez, Haley Luke, Sothear Maguire, Jane McArdle, Patrick F. McDonough, Caitrin W. Meschia, James F. Metso, Tiina Müller-Nurasyid, Martina O'Connor, Timothy D. O'Donnell, Martin Peddareddygari, Leema R. Pera, Joanna Perry, James A. Peters, Annette Putaala, Jukka Ray, Debashree Rexrode, Kathryn Ribasés Haro, Marta Rosand, Jonathan Rothwell, Peter M. Rundek, Tatjana Ryan, Kathleen A. Sacco, Ralph L. Salomaa, Veikko Sánchez Mora, Cristina Schmidt, Reinhold Sharma, Pankaj Slowik, Agnieszka Smith, Jennifer A. Smith, Nicholas L. Wassertheil-Smoller, Sylvia Söderholm, Martin Stine, O. Colin Strbian, Daniel Sudlow, Cathie L. M. Tatlisumak, Turgut Terao, Chikashi Thijs, Vincent Torres Águila, Nuria Paz Trégouët, David-Alexandre Tuladhar, Anil M. Veldink, Jan H. Walters, Robin G. Weir, David R. Woo, Daniel Worrall, Bradford B. Hong, Charles C. Ross, Owen A. Zand, Ramin de Leeuw, Frank-Erik Lindgren, Arne G. Pare, Guillaume Anderson, Christopher D. Markus, Hugh S. Jern, Christina Malik, Rainer Dichgans, Martin Mitchell, Braxton D. Kittner, Steven J. Early Onset Stroke Genetics Consortium of the International Stroke Genetics Consortium (ISGC) |
| author |
Jaworek, Thomas |
| author_facet |
Jaworek, Thomas Xu, Huichun Gaynor, Brady J. Cole, John W. Rannikmae, Kristiina Stanne, Tara M. Tomppo, Liisa Abedi, Vida Amouyel, Philippe Armstrong, Nicole D. Attia, John Bell, Steven Benavente, Oscar R. Boncoraglio, Giorgio B. Butterworth, Adam Carcel-Marquez, Jara Chen, Zhengming Chong, Michael Cruchaga, Carlos Cushman, Mary Danesh, John Debette, Stéphanie Duggan, David J. Durda, Jon Peter Engstrom, Gunnar Enzinger, Chris Faul, Jessica D. Fecteau, Natalie S. Fernandez-Cadenas, Israel Gieger, Christian Giese, Anne-Katrin Grewal, Raji P. Grittner, Ulrike Havulinna, Aki S. Heitsch, Laura Hochberg, Marc C. Holliday, Elizabeth Hu, Jie Ilinca, Andreea Irvin, Marguerite R. Jackson, Rebecca D. Jacob, Mina A. Rabionet Janssen, Raquel Jiménez Conde, Jordi Johnson, Julie A. Kamatani, Yoichiro Kardia, Sharon L. R. Koido, Masaru Kubo, Michiaki Lange, Leslie Lee, Jin-Moo Lemmens, Robin Levi, Christopher R. Li, Jiang Li, Liming Lin, Kuang Lopez, Haley Luke, Sothear Maguire, Jane McArdle, Patrick F. McDonough, Caitrin W. Meschia, James F. Metso, Tiina Müller-Nurasyid, Martina O'Connor, Timothy D. O'Donnell, Martin Peddareddygari, Leema R. Pera, Joanna Perry, James A. Peters, Annette Putaala, Jukka Ray, Debashree Rexrode, Kathryn Ribasés Haro, Marta Rosand, Jonathan Rothwell, Peter M. Rundek, Tatjana Ryan, Kathleen A. Sacco, Ralph L. Salomaa, Veikko Sánchez Mora, Cristina Schmidt, Reinhold Sharma, Pankaj Slowik, Agnieszka Smith, Jennifer A. Smith, Nicholas L. Wassertheil-Smoller, Sylvia Söderholm, Martin Stine, O. Colin Strbian, Daniel Sudlow, Cathie L. M. Tatlisumak, Turgut Terao, Chikashi Thijs, Vincent Torres Águila, Nuria Paz Trégouët, David-Alexandre Tuladhar, Anil M. Veldink, Jan H. Walters, Robin G. Weir, David R. Woo, Daniel Worrall, Bradford B. Hong, Charles C. Ross, Owen A. Zand, Ramin de Leeuw, Frank-Erik Lindgren, Arne G. Pare, Guillaume Anderson, Christopher D. Markus, Hugh S. Jern, Christina Malik, Rainer Dichgans, Martin Mitchell, Braxton D. Kittner, Steven J. Early Onset Stroke Genetics Consortium of the International Stroke Genetics Consortium (ISGC) |
| author_role |
author |
| author2 |
Xu, Huichun Gaynor, Brady J. Cole, John W. Rannikmae, Kristiina Stanne, Tara M. Tomppo, Liisa Abedi, Vida Amouyel, Philippe Armstrong, Nicole D. Attia, John Bell, Steven Benavente, Oscar R. Boncoraglio, Giorgio B. Butterworth, Adam Carcel-Marquez, Jara Chen, Zhengming Chong, Michael Cruchaga, Carlos Cushman, Mary Danesh, John Debette, Stéphanie Duggan, David J. Durda, Jon Peter Engstrom, Gunnar Enzinger, Chris Faul, Jessica D. Fecteau, Natalie S. Fernandez-Cadenas, Israel Gieger, Christian Giese, Anne-Katrin Grewal, Raji P. Grittner, Ulrike Havulinna, Aki S. Heitsch, Laura Hochberg, Marc C. Holliday, Elizabeth Hu, Jie Ilinca, Andreea Irvin, Marguerite R. Jackson, Rebecca D. Jacob, Mina A. Rabionet Janssen, Raquel Jiménez Conde, Jordi Johnson, Julie A. Kamatani, Yoichiro Kardia, Sharon L. R. Koido, Masaru Kubo, Michiaki Lange, Leslie Lee, Jin-Moo Lemmens, Robin Levi, Christopher R. Li, Jiang Li, Liming Lin, Kuang Lopez, Haley Luke, Sothear Maguire, Jane McArdle, Patrick F. McDonough, Caitrin W. Meschia, James F. Metso, Tiina Müller-Nurasyid, Martina O'Connor, Timothy D. O'Donnell, Martin Peddareddygari, Leema R. Pera, Joanna Perry, James A. Peters, Annette Putaala, Jukka Ray, Debashree Rexrode, Kathryn Ribasés Haro, Marta Rosand, Jonathan Rothwell, Peter M. Rundek, Tatjana Ryan, Kathleen A. Sacco, Ralph L. Salomaa, Veikko Sánchez Mora, Cristina Schmidt, Reinhold Sharma, Pankaj Slowik, Agnieszka Smith, Jennifer A. Smith, Nicholas L. Wassertheil-Smoller, Sylvia Söderholm, Martin Stine, O. Colin Strbian, Daniel Sudlow, Cathie L. M. Tatlisumak, Turgut Terao, Chikashi Thijs, Vincent Torres Águila, Nuria Paz Trégouët, David-Alexandre Tuladhar, Anil M. Veldink, Jan H. Walters, Robin G. Weir, David R. Woo, Daniel Worrall, Bradford B. Hong, Charles C. Ross, Owen A. Zand, Ramin de Leeuw, Frank-Erik Lindgren, Arne G. Pare, Guillaume Anderson, Christopher D. Markus, Hugh S. Jern, Christina Malik, Rainer Dichgans, Martin Mitchell, Braxton D. Kittner, Steven J. Early Onset Stroke Genetics Consortium of the International Stroke Genetics Consortium (ISGC) |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Isquèmia cerebral Genètica Embòlia i trombosi cerebral Cerebral ischemia Genetics Cerebral embolism and thrombosis |
| topic |
Isquèmia cerebral Genètica Embòlia i trombosi cerebral Cerebral ischemia Genetics Cerebral embolism and thrombosis |
| description |
Background and objectives: Current genome-wide association studies of ischemic stroke have focused primarily on late-onset disease. As a complement to these studies, we sought to identify the contribution of common genetic variants to risk of early-onset ischemic stroke. Methods: We performed a meta-analysis of genome-wide association studies of early-onset stroke (EOS), ages 18-59 years, using individual-level data or summary statistics in 16,730 cases and 599,237 nonstroke controls obtained across 48 different studies. We further compared effect sizes at associated loci between EOS and late-onset stroke (LOS) and compared polygenic risk scores (PRS) for venous thromboembolism (VTE) between EOS and LOS. Results: We observed genome-wide significant associations of EOS with 2 variants in ABO, a known stroke locus. These variants tag blood subgroups O1 and A1, and the effect sizes of both variants were significantly larger in EOS compared with LOS. The odds ratio (OR) for rs529565, tagging O1, was 0.88 (95% confidence interval [CI]: 0.85-0.91) in EOS vs 0.96 (95% CI: 0.92-1.00) in LOS, and the OR for rs635634, tagging A1, was 1.16 (1.11-1.21) for EOS vs 1.05 (0.99-1.11) in LOS; p-values for interaction = 0.001 and 0.005, respectively. Using PRSs, we observed that greater genetic risk for VTE, another prothrombotic condition, was more strongly associated with EOS compared with LOS (p = 0.008). Discussion: The ABO locus, genetically predicted blood group A, and higher genetic propensity for venous thrombosis are more strongly associated with EOS than with LOS, supporting a stronger role of prothrombotic factors in EOS. |
| publishDate |
2022 |
| dc.date.none.fl_str_mv |
2022 2025 2025 2025 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/2445/219351 |
| url |
https://hdl.handle.net/2445/219351 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Reproducció del document publicat a: https://doi.org/10.1212/WNL.0000000000201006 Neurology, 2022, vol. 99, num.16, p. E1738-E1754 https://doi.org/10.1212/WNL.0000000000201006 |
| dc.rights.none.fl_str_mv |
(c) American Academy of Neurology, 2022 info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
(c) American Academy of Neurology, 2022 |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
18 p. application/pdf |
| dc.publisher.none.fl_str_mv |
Lippincott, Williams & Wilkins. Wolters Kluwer Health |
| publisher.none.fl_str_mv |
Lippincott, Williams & Wilkins. Wolters Kluwer Health |
| dc.source.none.fl_str_mv |
Articles publicats en revistes (Genètica, Microbiologia i Estadística) reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| instname_str |
Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| reponame_str |
Recercat. Dipósit de la Recerca de Catalunya |
| collection |
Recercat. Dipósit de la Recerca de Catalunya |
| repository.name.fl_str_mv |
|
| repository.mail.fl_str_mv |
|
| _version_ |
1869420030070882304 |
| spelling |
Contribution of Common Genetic Variants to Risk of Early-Onset Ischemic StrokeJaworek, ThomasXu, HuichunGaynor, Brady J.Cole, John W.Rannikmae, KristiinaStanne, Tara M.Tomppo, LiisaAbedi, VidaAmouyel, PhilippeArmstrong, Nicole D.Attia, JohnBell, StevenBenavente, Oscar R.Boncoraglio, Giorgio B.Butterworth, AdamCarcel-Marquez, JaraChen, ZhengmingChong, MichaelCruchaga, CarlosCushman, MaryDanesh, JohnDebette, StéphanieDuggan, David J.Durda, Jon PeterEngstrom, GunnarEnzinger, ChrisFaul, Jessica D.Fecteau, Natalie S.Fernandez-Cadenas, IsraelGieger, ChristianGiese, Anne-KatrinGrewal, Raji P.Grittner, UlrikeHavulinna, Aki S.Heitsch, LauraHochberg, Marc C.Holliday, ElizabethHu, JieIlinca, AndreeaIrvin, Marguerite R.Jackson, Rebecca D.Jacob, Mina A.Rabionet Janssen, RaquelJiménez Conde, JordiJohnson, Julie A.Kamatani, YoichiroKardia, Sharon L. R.Koido, MasaruKubo, MichiakiLange, LeslieLee, Jin-MooLemmens, RobinLevi, Christopher R.Li, JiangLi, LimingLin, KuangLopez, HaleyLuke, SothearMaguire, JaneMcArdle, Patrick F.McDonough, Caitrin W.Meschia, James F.Metso, TiinaMüller-Nurasyid, MartinaO'Connor, Timothy D.O'Donnell, MartinPeddareddygari, Leema R.Pera, JoannaPerry, James A.Peters, AnnettePutaala, JukkaRay, DebashreeRexrode, KathrynRibasés Haro, MartaRosand, JonathanRothwell, Peter M.Rundek, TatjanaRyan, Kathleen A.Sacco, Ralph L.Salomaa, VeikkoSánchez Mora, CristinaSchmidt, ReinholdSharma, PankajSlowik, AgnieszkaSmith, Jennifer A.Smith, Nicholas L.Wassertheil-Smoller, SylviaSöderholm, MartinStine, O. ColinStrbian, DanielSudlow, Cathie L. M.Tatlisumak, TurgutTerao, ChikashiThijs, VincentTorres Águila, Nuria PazTrégouët, David-AlexandreTuladhar, Anil M.Veldink, Jan H.Walters, Robin G.Weir, David R.Woo, DanielWorrall, Bradford B.Hong, Charles C.Ross, Owen A.Zand, Raminde Leeuw, Frank-ErikLindgren, Arne G.Pare, GuillaumeAnderson, Christopher D.Markus, Hugh S.Jern, ChristinaMalik, RainerDichgans, MartinMitchell, Braxton D.Kittner, Steven J.Early Onset Stroke Genetics Consortium of the International Stroke Genetics Consortium (ISGC)Isquèmia cerebralGenèticaEmbòlia i trombosi cerebralCerebral ischemiaGeneticsCerebral embolism and thrombosisBackground and objectives: Current genome-wide association studies of ischemic stroke have focused primarily on late-onset disease. As a complement to these studies, we sought to identify the contribution of common genetic variants to risk of early-onset ischemic stroke. Methods: We performed a meta-analysis of genome-wide association studies of early-onset stroke (EOS), ages 18-59 years, using individual-level data or summary statistics in 16,730 cases and 599,237 nonstroke controls obtained across 48 different studies. We further compared effect sizes at associated loci between EOS and late-onset stroke (LOS) and compared polygenic risk scores (PRS) for venous thromboembolism (VTE) between EOS and LOS. Results: We observed genome-wide significant associations of EOS with 2 variants in ABO, a known stroke locus. These variants tag blood subgroups O1 and A1, and the effect sizes of both variants were significantly larger in EOS compared with LOS. The odds ratio (OR) for rs529565, tagging O1, was 0.88 (95% confidence interval [CI]: 0.85-0.91) in EOS vs 0.96 (95% CI: 0.92-1.00) in LOS, and the OR for rs635634, tagging A1, was 1.16 (1.11-1.21) for EOS vs 1.05 (0.99-1.11) in LOS; p-values for interaction = 0.001 and 0.005, respectively. Using PRSs, we observed that greater genetic risk for VTE, another prothrombotic condition, was more strongly associated with EOS compared with LOS (p = 0.008). Discussion: The ABO locus, genetically predicted blood group A, and higher genetic propensity for venous thrombosis are more strongly associated with EOS than with LOS, supporting a stronger role of prothrombotic factors in EOS.Lippincott, Williams & Wilkins. Wolters Kluwer Health2025202520222025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion18 p.application/pdfhttps://hdl.handle.net/2445/219351Articles publicats en revistes (Genètica, Microbiologia i Estadística)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1212/WNL.0000000000201006Neurology, 2022, vol. 99, num.16, p. E1738-E1754https://doi.org/10.1212/WNL.0000000000201006(c) American Academy of Neurology, 2022info:eu-repo/semantics/openAccessoai:recercat.cat:2445/2193512026-05-29T05:05:01Z |
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15.811543 |