1. Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes
- Author
-
Pulit, Sara L., Weng, Lu-Chen, McArdle, Patrick F, Trinquart, Ludovic, Choi, Seung Hoan, Mitchell, Braxton D., Rosand, Jonathan, de Bakker, Paul I W, Benjamin, Emelia J, Ellinor, Patrick T, 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., Müller-Nurasyid, Martina, Smith, J. Gustav, Brody, Jennifer A., Niemeijer, Maartje N., Dörr, Marcus, Trompet, Stella, Huffman, Jennifer, Gustafsson, Stefan, Schurmann, Claudia, Kleber, Marcus E., Lyytikäinen, Leo-Pekka, Seppälä, Ilkka, Malik, Rainer, Horimoto, Andrea R. V. R., Perez, Marco, Sinisalo, Juha, Aeschbacher, Stefanie, Thériault, Sébastien, Yao, Jie, Radmanesh, Farid, Weiss, Stefan, Teumer, Alexander, Clauss, Sebastian, Deo, Rajat, Rader, Daniel J., Shah, Svati, 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., Kähönen, 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, Orho-Melander, arju, 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., Völker, Uwe, Jöckel, Karl-Heinz, Sinner, Moritz F., Lin, Henry J., Guo, Xiuqing, Dichgans, Martin, Ingelsson, Erik, Kooperberg, Charles, Melander, Olle, Loos, Ruth J. F., Laurikka, Jari, Conen, David, Harst, Pim van der, Lokki, Marja-Liisa, Kathiresan, Sekar, Pereira, Alexandre, Jukema, J. Wouter, Hayward, Caroline, Rotter, Jerome I., März, Winfried, Lehtimäki, Terho, Stricker, Bruno H., Chung, Mina K., Felix, Stephan B., Gudnason, Vilmundur, Alonso, Alvaro, Roden, Dan M., Sun, Albert, Anderson, Christopher D., Kääb, Stefan, Hopewell, Jemma C., Debette, Stephanie, Chauhan, Ganesh, Yang, Qiong, Worrall, Bradford B., Paré, Guillaume, Kamatani, Yoichiro, Hagemeijer, Yanick P., Verweij, Niek, Taylor, Kent D., Campbell, Archie, Magnusson, Patrik K., Porteous, David, Hocking, Lynne J., Vlachopoulou, Efthymia, Pedersen, Nancy L., Nikus, Kjell, Chasman, Daniel I., Heckbert, Susan R., Benjamin, Emelia J., Tanaka, Toshihiro, Lunetta, Kathryn L., Lubitz, Steven A., Ellinor, Patrick T., Smoller, Sylvia, Sorkin, John, Wang, Xingwu, Selim, Magdy, Pikula, Aleksandra, Wolf, Philip, Seshadri, Sudha, Bakker, Paul de, 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, Meschia, James, Brott, Thomas, Pare, Guillaume, 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, Martin, Juan Jose, 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, Cathie, Sudlow, 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, John, Attia, 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, Sheth, Kevin, Cardiovascular Centre (CVC), Department of Medicine, Clinicum, Transplantation Laboratory, Medicum, Neurologian yksikkö, Department of Neurosciences, University of Helsinki, Doctoral Programme in Clinical Research, HUS Neurocenter, Epidemiology, Internal Medicine, Klinische Neurowetenschappen, RS: CARIM - R3.03 - Cerebral small vessel disease, and MUMC+: MA Med Staf Spec Neurologie (9)
- Subjects
Medizin ,030204 cardiovascular system & hematology ,VARIANTS ,3124 Neurology and psychiatry ,0302 clinical medicine ,Epidemiology ,Genotype ,EPIDEMIOLOGY ,Stroke ,Genetics (clinical) ,0303 health sciences ,Aspirin ,Atrial fibrillation ,ASSOCIATION ,3. Good health ,LIFETIME RISK ,ISCHEMIC-STROKE ,Cardiology ,Biomarker (medicine) ,Medical genetics ,BURDEN ,Medical Genetics ,Life Sciences & Biomedicine ,medicine.drug ,medicine.medical_specialty ,Clinical Neurology ,Single-nucleotide polymorphism ,Article ,03 medical and health sciences ,Internal medicine ,Genetic predisposition ,medicine ,SNP ,cardiovascular diseases ,Genotyping ,030304 developmental biology ,Genetic association ,Medicinsk genetik ,Science & Technology ,business.industry ,3112 Neurosciences ,Heritability ,medicine.disease ,PREVENTION ,ASPIRIN ,Neurology (clinical) ,Neurosciences & Neurology ,business ,030217 neurology & neurosurgery ,CAUSATIVE CLASSIFICATION - Abstract
ObjectiveWe sought to assess whether genetic risk factors for atrial fibrillation (AF) can explain cardioembolic stroke risk.MethodsWe 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.ResultsWe 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 p < 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, p = 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, p = 0.004), but no other primary stroke subtypes (all p > 0.1).ConclusionsGenetic 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.
- Published
- 2018