Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes

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Pulit, Sara L, Weng, Lu-Chen, McArdle, Patrick F, Trinquart, Ludovic, Choi, Seung Hoan, Mitchell, Braxton D, Rosand, Jonathan, de Bakker, Paul IW, Benjamin, Emelia J, Ellinor, Patrick T et al (show 351 more authors) , Kittner, Steven J, Lubitz, Steven A, Anderson, Christopher D, Christophersen, Ingrid E, Rienstra, Michiel, Roselli, Carolina, Yin, Xiaoyan, Geelhoed, Bastiaan, Barnard, John, Lin, Honghuang, Arking, Dan E, Smith, Albert V, Albert, Christine M, Chaffin, Mark, Tucker, Nathan R, Li, Molong, Klarin, Derek, Bihlmeyer, Nathan A, Low, Siew-Kee, Weeke, Peter E, Mueller-Nurasyid, Martina, Smith, J Gustav, Brody, Jennifer A, Niemeijer, Maartje N, Doerr, Marcus, Trompet, Stella, Huffman, Jennifer, Gustafsson, Stefan, Schurmann, Claudia, Kleber, Marcus E, Lyytikainen, Leo-Pekka, Seppala, Ilkka, Malik, Rainer, Horimoto, Andrea RVR, Perez, Marco, Sinisalo, Juha, Aeschbacher, Stefanie, Theriault, Sebastien, Yao, Jie, Radmanesh, Farid, Weiss, Stefan, Teumer, Alexander, Clauss, Sebastian, Deo, Rajat, Rader, Daniel J, Shah, Svati, Sun, Albert, Hopewell, Jemma C, Debette, Stephanie, Chauhan, Ganesh, Yang, Qiong, Worrall, Bradford B, Pare, Guillaume, Kamatani, Yoichiro, Hagemeijer, Yanick P, Verweij, Niek, Siland, Joylene E, Kubo, Michiaki, Smith, Jonathan D, Van Wagoner, David R, Bis, Joshua C, Perz, Siegfried, Psaty, Bruce M, Ridker, Paul M, Magnani, Jared W, Harris, Tamara B, Launer, Lenore J, Shoemaker, M Benjamin, Padmanabhan, Sandosh, Haessler, Jeffrey, Bartz, Traci M, Waldenberger, Melanie, Lichtner, Peter, Arendt, Marina, Krieger, Jose E, Kahonen, Mika, Risch, Lorenz, Mansur, Alfredo J, Peters, Annette, Smith, Blair H, Lind, Lars, Scott, Stuart A, Lu, Yingchang, Bottinger, Erwin B, Hernesniemi, Jussi, Lindgren, Cecilia M, Wong, Jorge A, Huang, Jie, Eskola, Markku, Morris, Andrew P, Ford, Ian, Reiner, Alex P, Delgado, Graciela, Chen, Lin Y, Chen, Yii-Der Ida, Sandhu, Roopinder K, Li, Man, Boerwinkle, Eric, Eisele, Lewin, Lannfelt, Lars, Rost, Natalia, Taylor, Kent D, Campbell, Archie, Magnusson, Patrik K, Porteous, David, Hocking, Lynne J, Vlachopoulou, Efthymia, Pedersen, Nancy L, Nikus, Kjell, Orho-Melander, Marju, Hamsten, Anders, Heeringa, Jan, Denny, Joshua C, Kriebel, Jennifer, Darbar, Dawood, Newton-Cheh, Christopher, Shaffer, Christian, Macfarlane, Peter W, Heilmann, Stefanie, Almgren, Peter, Huang, Paul L, Sotoodehnia, Nona, Soliman, Elsayed Z, Uitterlinden, Andre G, Hofman, Albert, Franco, Oscar H, Voelker, Uwe, Joeckel, Karl-Heinz, Sinner, Moritz F, Lin, Henry J, Guo, Xiuqing, Dichgans, Martin, Ingelsson, Erik, Kooperberg, Charles, Melander, Olle, Loos, Ruth JF, Laurikka, Jari, Conen, David, van der Harst, Pim, Lokki, Marja-Liisa, Kathiresan, Sekar, Pereira, Alexandre, Jukema, J Wouter, Hayward, Caroline, Rotter, Jerome I, Maerz, Winfried, Lehtimaki, Terho, Stricker, Bruno H, Chung, Mina K, Felix, Stephan B, Gudnason, Vilmundur, Alonso, Alvaro, Roden, Dan M, Kaeaeb, Stefan, Chasman, Daniel I, Heckbert, Susan R, Tanaka, Toshihiro, Lunetta, Kathryn L, Smoller, Sylvia, Sorkin, John, Wang, Xingwu, Selim, Magdy, Pikula, Aleksandra, Wolf, Philip, Seshadri, Sudha, de Bakker, Paul, Chasman, Daniel, Rexrode, Kathryn, Chen, Ida, Rotter, Jerome, Luke, May, Sale, Michelle, Lee, Tsong-Hai, Chang, Ku-Chou, Elkind, Mitchell, Goldstein, Larry, James, Michael Luke, Breteler, Monique, O'Donnell, Chris, Leys, Didier, Carty, Cara, Kidwell, Chelsea, Olesen, Jes, Sharma, Pankaj, Rich, Stephen, Tatlisumak, Turgot, Happola, Olli, Bijlenga, Philippe, Soriano, Carolina, Giralt, Eva, Roquer, Jaume, Jimenez-Conde, Jordi, Cotlarcius, Ioana, Hardy, John, Korostynski, Michal, Boncoraglio, Giorgio, Ballabio, Elena, Parati, Eugenio, Mateusz, Adamski, Urbanik, Andrzej, Dziedzic, Tomasz, Jagiella, Jeremiasz, Gasowski, Jerzy, Wnuk, Marcin, Olszanecki, Rafael, Pera, Joanna, Slowik, Agnieszka, Juchniewicz, Karol Jozef, Levi, Christopher, Nyquist, Paul, Cendes, Iscia, Cabral, Norberto, Franca, Paulo, Goncalves, Anderson, Keller, Lina, Crisby, Milita, Kostulas, Konstantinos, Lemmens, Robin, Ahmadi, Kourosh, Opherk, Christian, Duering, Marco, Gonik, Mariya, Staals, Julie, Burri, Philippe, Sadr-Nabavi, Ariane, Romero, Javier, Biffi, Alessandro, Anderson, Chris, Falcone, Guido, Brouwers, Bart, Du, Rose, Kourkoulis, Christina, Battey, Thomas, Lubitz, Steven, Mueller-Myhsok, Bertram ORCID: 0000-0002-0719-101X, Meschia, James, Brott, Thomas, Pichler, Alexander, Enzinger, Christian, Schmidt, Helena, Schmidt, Reinhold, Seiler, Stephan, Blanton, Susan, Yamada, Yoshiji, Bersano, Anna, Rundek, Tatjana, Sacco, Ralph, Chan, Yu-Feng Yvonne, Gschwendtner, Andreas, Deng, Zhen, Barr, Taura, Gwinn, Katrina, Corriveau, Roderick, Singleton, Andrew, Waddy, Salina, Launer, Lenore, Chen, Christopher, Le, Kim En, Lee, Wei Ling, Tan, Eng King, Olugbodi, Akintomi, Rothwell, Peter, Schilling, Sabrina, Mok, Vincent, Lebedeva, Elena, Jern, Christina, Jood, Katarina, Olsson, Sandra, Kim, Helen, Lee, Chaeyoung, Kilarski, Laura, Markus, Hugh, Peycke, Jennifer, Bevan, Steve, Sheu, Wayne, Chiou, Hung Yi, Chern, Joseph, Giraldo, Elias, Taqi, Muhammad, Jain, Vivek, Lam, Olivia, Howard, George, Woo, Daniel, Kittner, Steven, Mitchell, Braxton, Cole, John, O'Connell, Jeff, Milewicz, Dianna, Illoh, Kachikwu, Worrall, Bradford, Stine, Colin, Karaszewski, Bartosz, Werring, David, Sofat, Reecha, Smalley, June, Lindgren, Arne, Hansen, Bjorn, Norrving, Bo, Smith, Gustav, Jose Martin, Juan, Thijs, Vincent, Klijn, Karin, van't Hof, Femke, Algra, Ale, Macleod, Mary, Perry, Rodney, Arnett, Donna, Pezzini, Alessandro, Padovani, Alessandro, Cramer, Steve, Fisher, Mark, Saleheen, Danish, Broderick, Joseph, Kissela, Brett, Doney, Alex, Sudlow, Cathie, Rannikmae, Kristiina, Silliman, Scott, McDonough, Caitrin, Walters, Matthew, Pedersen, Annie, Nakagawa, Kazuma, Chang, Christy, Dobbins, Mark, McArdle, Patrick, Chang, Yu-Ching, Brown, Robert, Brown, Devin, Holliday, Elizabeth, Kalaria, Raj, Maguire, Jane, Attia, John, Farrall, Martin, Giese, Anne-Katrin, Fornage, Myriam, Majersik, Jennifer, Cushman, Mary, Keene, Keith, Bennett, Siiri, Tirschwell, David, Psaty, Bruce, Reiner, Alex, Longstreth, Will, Spence, David, Montaner, Joan, Fernandez-Cadenas, Israel, Langefeld, Carl, Bushnell, Cheryl, Heitsch, Laura, Lee, Jin-Moo and Sheth, Kevin (2018) Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes. NEUROLOGY-GENETICS, 4 (6). e293-. ISSN 2376-7839, 2376-7839

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Abstract

<h4>Objective</h4>We sought to assess whether genetic risk factors for atrial fibrillation (AF) can explain cardioembolic stroke risk.<h4>Methods</h4>We evaluated genetic correlations between a previous genetic study of AF and AF in the presence of cardioembolic stroke using genome-wide genotypes from the Stroke Genetics Network (N = 3,190 AF cases, 3,000 cardioembolic stroke cases, and 28,026 referents). We tested whether a previously validated AF polygenic risk score (PRS) associated with cardioembolic and other stroke subtypes after accounting for AF clinical risk factors.<h4>Results</h4>We observed a strong correlation between previously reported genetic risk for AF, AF in the presence of stroke, and cardioembolic stroke (Pearson r = 0.77 and 0.76, respectively, across SNPs with <i>p</i> < 4.4 × 10^-4 in the previous AF meta-analysis). An AF PRS, adjusted for clinical AF risk factors, was associated with cardioembolic stroke (odds ratio [OR] per SD = 1.40, <i>p</i> = 1.45 × 10^-48), explaining ∼20% of the heritable component of cardioembolic stroke risk. The AF PRS was also associated with stroke of undetermined cause (OR per SD = 1.07, <i>p</i> = 0.004), but no other primary stroke subtypes (all <i>p</i> > 0.1).<h4>Conclusions</h4>Genetic risk of AF is associated with cardioembolic stroke, independent of clinical risk factors. Studies are warranted to determine whether AF genetic risk can serve as a biomarker for strokes caused by AF.

Item Type:	Article
Uncontrolled Keywords:	31 Biological Sciences, 32 Biomedical and Clinical Sciences, 3105 Genetics, Prevention, Human Genome, Heart Disease, Genetics, Cardiovascular, Clinical Research, Stroke, Brain Disorders, Cerebrovascular, 2.1 Biological and endogenous factors, Stroke
Depositing User:	Symplectic Admin
Date Deposited:	19 Feb 2020 13:22
Last Modified:	03 Jan 2025 19:21
DOI:	10.1212/NXG.0000000000000293
Open Access URL:	https://doi.org/10.1212/NXG.0000000000000293
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3075727