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Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes
Authors :
Pulit, SL Weng, L-C McArdle, PF Trinquart, L Choi, SH Mitchell, BD Rosand, J de Bakker, PIW Benjamin, EJ Ellinor, PT Kittner, SJ Lubitz, SA Anderson, CD Christophersen, IE Rienstra, M Roselli, C Yin, X Geelhoed, B Barnard, J Lin, H Arking, DE Smith, A Albert, CM Chaffin, M Tucker, NR Li, M Klarin, D Bihlmeyer, NA Low, S-K Weeke, PE Mueller-Nurasyid, M Smith, JG Brody, JA Niemeijer, MN Doerr, M Trompet, S Huffman, J Gustafsson, S Schurmann, C Kleber, ME Lyytikainen, L-P Seppala, I Malik, R Horimoto, ARVR Perez, M Sinisalo, J Aeschbacher, S Theriault, S Yao, J Radmanesh, F Weiss, S Teumer, A Clauss, S Deo, R Rader, DJ Shah, S Sun, A Hopewell, JC Debette, S Chauhan, G Yang, Q Worrall, BB Pare, G Kamatani, Y Hagemeijer, YP Verweij, N Siland, JE Kubo, M Smith, JD Van Wagoner, DR Bis, JC Perz, S Psaty, BM Ridker, PM Magnani, JW Harris, TB Launer, LJ Shoemaker, MB Padmanabhan, S Haessler, J Bartz, TM Waldenberger, M Lichtner, P Arendt, M Krieger, JE Kahonen, M Risch, L Mansur, AJ Peters, A Smith, BH Lind, L Scott, SA Lu, Y Bottinger, EB Hernesniemi, J Lindgren, CM Wong, JA Huang, J Eskola, M Morris, AP Ford, I Reiner, AP Delgado, G Chen, LY Chen, Y-DI Sandhu, RK Boerwinkle, E Eisele, L Lannfelt, L Rost, N Taylor, KD Campbell, A Magnusson, PK Porteous, D Hocking, LJ Vlachopoulou, E Pedersen, NL Nikus, K Orho-Melander, M Hamsten, A Heeringa, J Denny, JC Kriebel, J Darbar, D Newton-Cheh, C Shaffer, C Macfarlane, PW Heilmann, S Almgren, P Huang, PL Sotoodehnia, N Soliman, EZ Uitterlinden, AG Hofman, A Franco, OH Voelker, U Joeckel, K-H Sinner, MF Lin, HJ Guo, X Dichgans, M Ingelsson, E Kooperberg, C Melander, O Loos, RJF Laurikka, J Conen, D van der Harst, P Lokki, M-L Kathiresan, S Pereira, A Jukema, JW Hayward, C Rotter, J Maerz, W Lehtimaki, T Stricker, BH Chung, MK Felix, SB Gudnason, V Alonso, A Roden, DM Kaeaeb, S Chasman, D Heckbert, SR Tanaka, T Lunetta, KL Smoller, S Sorkin, J Wang, X Selim, M Pikula, A Wolf, P Seshadri, S de Bakker, P Rexrode, K Chen, I Luke, M Sale, M Lee, T-H Chang, K-C Elkind, M Goldstein, L James, ML Breteler, M O'Donnell, C Leys, D Carty, C Kidwell, C Olesen, J Sharma, P Rich, S Tatlisumak, T Happola, O Bijlenga, P Soriano, C Giralt, E Roquer, J Jimenez-Conde, J Cotlarcius, I Hardy, J Korostynski, M Boncoraglio, G Ballabio, E Parati, E Mateusz, A Urbanik, A Dziedzic, T Jagiella, J Gasowski, J Wnuk, M Olszanecki, R Pera, J Slowik, A Juchniewicz, KJ Levi, C Nyquist, P Cendes, I Cabral, N Franca, P Goncalves, A Keller, L Crisby, M Kostulas, K Lemmens, R Ahmadi, K Opherk, C Duering, M Gonik, M Staals, J Burri, P Sadr-Nabavi, A Romero, J Biffi, A Anderson, C Falcone, G Brouwers, B Du, R Kourkoulis, C Battey, T Lubitz, S Mueller-Myhsok, B Meschia, J Brott, T Pichler, A Enzinger, C Schmidt, H Schmidt, R Seiler, S Blanton, S Yamada, Y Bersano, A Rundek, T Sacco, R Chan, Y-FY Gschwendtner, A Deng, Z Barr, T Gwinn, K Corriveau, R Singleton, A Waddy, S Launer, L Chen, C Le, KE Lee, WL Tan, EK Olugbodi, A Rothwell, P Schilling, S Mok, V Lebedeva, E Jern, C Jood, K Olsson, S Kim, H Lee, C Kilarski, L Markus, H Peycke, J Bevan, S Sheu, W Chiou, HY Chern, J Giraldo, E Taqi, M Jain, V Lam, O Howard, G Woo, D Kittner, S Mitchell, B Cole, J O'Connell, J Milewicz, D Illoh, K Worrall, B Stine, C Karaszewski, B Werring, D Sofat, R Smalley, J Lindgren, A Hansen, B Norrving, B Smith, G Jose Martin, J Thijs, V Klijn, K van't Hof, F Algra, A Macleod, M Perry, R Arnett, D Pezzini, A Padovani, A Cramer, S Fisher, M Saleheen, D Broderick, J Kissela, B Doney, A Sudlow, C Rannikmae, K Silliman, S McDonough, C Walters, M Pedersen, A Nakagawa, K Chang, C Dobbins, M McArdle, P Chang, Y-C Brown, R Brown, D Holliday, E Kalaria, R Maguire, J Attia, J Farrall, M Giese, A-K Fornage, M Majersik, J Cushman, M Keene, K Bennett, S Tirschwell, D Psaty, B Reiner, A Longstreth, W Spence, D Montaner, J Fernandez-Cadenas, I Langefeld, C Bushnell, C Heitsch, L Lee, J-M Sheth, K Pulit, SL Weng, L-C McArdle, PF Trinquart, L Choi, SH Mitchell, BD Rosand, J de Bakker, PIW Benjamin, EJ Ellinor, PT Kittner, SJ Lubitz, SA Anderson, CD Christophersen, IE Rienstra, M Roselli, C Yin, X Geelhoed, B Barnard, J Lin, H Arking, DE Smith, A Albert, CM Chaffin, M Tucker, NR Li, M Klarin, D Bihlmeyer, NA Low, S-K Weeke, PE Mueller-Nurasyid, M Smith, JG Brody, JA Niemeijer, MN Doerr, M Trompet, S Huffman, J Gustafsson, S Schurmann, C Kleber, ME Lyytikainen, L-P Seppala, I Malik, R Horimoto, ARVR Perez, M Sinisalo, J Aeschbacher, S Theriault, S Yao, J Radmanesh, F Weiss, S Teumer, A Clauss, S Deo, R Rader, DJ Shah, S Sun, A Hopewell, JC Debette, S Chauhan, G Yang, Q Worrall, BB Pare, G Kamatani, Y Hagemeijer, YP Verweij, N Siland, JE Kubo, M Smith, JD Van Wagoner, DR Bis, JC Perz, S Psaty, BM Ridker, PM Magnani, JW Harris, TB Launer, LJ Shoemaker, MB Padmanabhan, S Haessler, J Bartz, TM Waldenberger, M Lichtner, P Arendt, M Krieger, JE Kahonen, M Risch, L Mansur, AJ Peters, A Smith, BH Lind, L Scott, SA Lu, Y Bottinger, EB Hernesniemi, J Lindgren, CM Wong, JA Huang, J Eskola, M Morris, AP Ford, I Reiner, AP Delgado, G Chen, LY Chen, Y-DI Sandhu, RK Boerwinkle, E Eisele, L Lannfelt, L Rost, N Taylor, KD Campbell, A Magnusson, PK Porteous, D Hocking, LJ Vlachopoulou, E Pedersen, NL Nikus, K Orho-Melander, M Hamsten, A Heeringa, J Denny, JC Kriebel, J Darbar, D Newton-Cheh, C Shaffer, C Macfarlane, PW Heilmann, S Almgren, P Huang, PL Sotoodehnia, N Soliman, EZ Uitterlinden, AG Hofman, A Franco, OH Voelker, U Joeckel, K-H Sinner, MF Lin, HJ Guo, X Dichgans, M Ingelsson, E Kooperberg, C Melander, O Loos, RJF Laurikka, J Conen, D van der Harst, P Lokki, M-L Kathiresan, S Pereira, A Jukema, JW Hayward, C Rotter, J Maerz, W Lehtimaki, T Stricker, BH Chung, MK Felix, SB Gudnason, V Alonso, A Roden, DM Kaeaeb, S Chasman, D Heckbert, SR Tanaka, T Lunetta, KL Smoller, S Sorkin, J Wang, X Selim, M Pikula, A Wolf, P Seshadri, S de Bakker, P Rexrode, K Chen, I Luke, M Sale, M Lee, T-H Chang, K-C Elkind, M Goldstein, L James, ML Breteler, M O'Donnell, C Leys, D Carty, C Kidwell, C Olesen, J Sharma, P Rich, S Tatlisumak, T Happola, O Bijlenga, P Soriano, C Giralt, E Roquer, J Jimenez-Conde, J Cotlarcius, I Hardy, J Korostynski, M Boncoraglio, G Ballabio, E Parati, E Mateusz, A Urbanik, A Dziedzic, T Jagiella, J Gasowski, J Wnuk, M Olszanecki, R Pera, J Slowik, A Juchniewicz, KJ Levi, C Nyquist, P Cendes, I Cabral, N Franca, P Goncalves, A Keller, L Crisby, M Kostulas, K Lemmens, R Ahmadi, K Opherk, C Duering, M Gonik, M Staals, J Burri, P Sadr-Nabavi, A Romero, J Biffi, A Anderson, C Falcone, G Brouwers, B Du, R Kourkoulis, C Battey, T Lubitz, S Mueller-Myhsok, B Meschia, J Brott, T Pichler, A Enzinger, C Schmidt, H Schmidt, R Seiler, S Blanton, S Yamada, Y Bersano, A Rundek, T Sacco, R Chan, Y-FY Gschwendtner, A Deng, Z Barr, T Gwinn, K Corriveau, R Singleton, A Waddy, S Launer, L Chen, C Le, KE Lee, WL Tan, EK Olugbodi, A Rothwell, P Schilling, S Mok, V Lebedeva, E Jern, C Jood, K Olsson, S Kim, H Lee, C Kilarski, L Markus, H Peycke, J Bevan, S Sheu, W Chiou, HY Chern, J Giraldo, E Taqi, M Jain, V Lam, O Howard, G Woo, D Kittner, S Mitchell, B Cole, J O'Connell, J Milewicz, D Illoh, K Worrall, B Stine, C Karaszewski, B Werring, D Sofat, R Smalley, J Lindgren, A Hansen, B Norrving, B Smith, G Jose Martin, J Thijs, V Klijn, K van't Hof, F Algra, A Macleod, M Perry, R Arnett, D Pezzini, A Padovani, A Cramer, S Fisher, M Saleheen, D Broderick, J Kissela, B Doney, A Sudlow, C Rannikmae, K Silliman, S McDonough, C Walters, M Pedersen, A Nakagawa, K Chang, C Dobbins, M McArdle, P Chang, Y-C Brown, R Brown, D Holliday, E Kalaria, R Maguire, J Attia, J Farrall, M Giese, A-K Fornage, M Majersik, J Cushman, M Keene, K Bennett, S Tirschwell, D Psaty, B Reiner, A Longstreth, W Spence, D Montaner, J Fernandez-Cadenas, I Langefeld, C Bushnell, C Heitsch, L Lee, J-M Sheth, K
Publication Year :
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 × 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). 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.
Details
Database :
OAIster
Publication Type :
Electronic Resource
Accession number :
edsoai.on1315677968
Document Type :
Electronic Resource