| Title: |
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 |
| Publisher Information: |
LIPPINCOTT WILLIAMS & WILKINS |
| Publication Year: |
2018 |
| Collection: |
The University of Melbourne: Digital Repository |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
2376-7839 |
| Relation: |
pii: NG2018008771; https://hdl.handle.net/11343/253799 |
| Availability: |
https://hdl.handle.net/11343/253799 |
| Rights: |
https://creativecommons.org/licenses/by-nc-nd/4.0 ; CC BY-NC-ND |
| Accession Number: |
edsbas.196432BF |
| Database: |
BASE |