Title: | Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes |
Authors: | PULIT, Sara L.; WENG, Lu-Chen; MCARDLE, Patrick F.; TRINQUART, Ludovic; CHOI, Seung Hoan; MITCHELL, Braxton D.; ROSAND, Jonathan; BAKKER, Paul I. W. de; 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.; V, Albert Smith; 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 R. V. R.; 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.; WAGONER, David R. Van; 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 J. F.; LAURIKKA, Jari; CONEN, David; HARST, Pim van der; LOKKI, Marja-Liisa; KATHIRESAN, Sekar; PEREIRA, Alexandre; JUKEMA, J. Wouter; HAYWARD, Caroline; I, Jerome Rotter; MAERZ, Winfried; LEHTIMAKI, Terho; STRICKER, Bruno H.; CHUNG, Mina K.; FELIX, Stephan B.; GUDNASON, Vilmundur; ALONSO, Alvaro; RODEN, Dan M.; KAEAEB, Stefan; I, Daniel Chasman; HECKBERT, Susan R.; TANAKA, Toshihiro; LUNETTA, Kathryn L.; 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; 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; HOF, Femke van't; 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; SHETH, Kevin |
Citation: | NEUROLOGY-GENETICS, v.4, n.6, article ID UNSP e293, 8p, 2018 |
Abstract: | Objective We sought to assess whether genetic risk factors for atrial fibrillation (AF) can explain cardioembolic stroke risk. Methods 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. Results 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 p < 4.4 x 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 x 10(-48)), explaining similar to 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). Conclusions 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. |
Appears in Collections: | Artigos e Materiais de Revistas Científicas - FM/MCP Departamento de Cardio-Pneumologia - FM/MCP Artigos e Materiais de Revistas Científicas - HC/InCor Instituto do Coração - HC/InCor Artigos e Materiais de Revistas Científicas - LIM/13 LIM/13 - Laboratório de Genética e Cardiologia Molecular Artigos e Materiais de Revistas Científicas - ODS/03 ODS/03 - Saúde e bem-estar |
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