Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes NEUROLOGY-GENETICS Pulit, S. L., Weng, L., McArdle, P. F., Trinquart, L., Choi, S., Mitchell, B. D., Rosand, J., de Bakker, P. W., Benjamin, E. J., Ellinor, P. T., Kittner, S. J., Lubitz, S. A., Anderson, C. D., Christophersen, I. E., Rienstra, M., Roselli, C., Yin, X., Geelhoed, B., Barnard, J., Lin, H., Arking, D. E., Smith, A., Albert, C. M., Chaffin, M., Tucker, N. R., Li, M., Klarin, D., Bihlmeyer, N. A., Low, S., Weeke, P. E., Mueller-Nurasyid, M., Smith, J., Brody, J. A., Niemeijer, M. N., Doerr, M., Trompet, S., Huffman, J., Gustafsson, S., Schurmann, C., Kleber, M. E., Lyytikainen, L., Seppala, I., Malik, R., Horimoto, A. R., Perez, M., Sinisalo, J., Aeschbacher, S., Theriault, S., Yao, J., Radmanesh, F., Weiss, S., Teumer, A., Clauss, S., Deo, R., Rader, D. J., Shah, S., Sun, A., Hopewell, J. C., Debette, S., Chauhan, G., Yang, Q., Worrall, B. B., Pare, G., Kamatani, Y., Hagemeijer, Y. P., Verweij, N., Siland, J. E., Kubo, M., Smith, J. D., Van Wagoner, D. R., Bis, J. C., Perz, S., Psaty, B. M., Ridker, P. M., Magnani, J. W., Harris, T. B., Launer, L. J., Shoemaker, M., Padmanabhan, S., Haessler, J., Bartz, T. M., Waldenberger, M., Lichtner, P., Arendt, M., Krieger, J. E., Kahonen, M., Risch, L., Mansur, A. J., Peters, A., Smith, B. H., Lind, L., Scott, S. A., Lu, Y., Bottinger, E. B., Hernesniemi, J., Lindgren, C. M., Wong, J. A., Huang, J., Eskola, M., Morris, A. P., Ford, I., Reiner, A. P., Delgado, G., Chen, L. Y., Chen, Y., Sandhu, R. K., Li, M., Boerwinkle, E., Eisele, L., Lannfelt, L., Rost, N., Taylor, K. D., Campbell, A., Magnusson, P. K., Porteous, D., Hocking, L. J., Vlachopoulou, E., Pedersen, N. L., Nikus, K., Orho-Melander, M., Hamsten, A., Heeringa, J., Denny, J. C., Kriebel, J., Darbar, D., Newton-Cheh, C., Shaffer, C., Macfarlane, P. W., Heilmann, S., Almgren, P., Huang, P. L., Sotoodehnia, N., Soliman, E. Z., Uitterlinden, A. G., Hofman, A., Franco, O. H., Voelker, U., Joeckel, K., Sinner, M. F., Lin, H. J., Guo, X., Dichgans, M., Ingelsson, E., Kooperberg, C., Melander, O., Loos, R. F., Laurikka, J., Conen, D., van der Harst, P., Lokki, M., Kathiresan, S., Pereira, A., Jukema, J., Hayward, C., Rotter, J., Maerz, W., Lehtimaki, T., Stricker, B. H., Chung, M. K., Felix, S. B., Gudnason, V., Alonso, A., Roden, D. M., Kaeaeb, S., Chasman, D., Heckbert, S. R., Tanaka, T., Lunetta, K. L., Smoller, S., Sorkin, J., Wang, X., Selim, M., Pikula, A., Wolf, P., Seshadri, S., de Bakker, P., Chasman, D., Rexrode, K., Chen, I., Rotter, J., Luke, M., Sale, M., Lee, T., Chang, K., Elkind, M., Goldstein, L., James, M., 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, K., 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., Gschwendtner, A., Deng, Z., Barr, T., Gwinn, K., Corriveau, R., Singleton, A., Waddy, S., Launer, L., Chen, C., Le, K., Lee, W., Tan, E., 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, H., 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., Brown, R., Brown, D., Holliday, E., Kalaria, R., Maguire, J., Attia, J., Farrall, M., Giese, A., 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., Sheth, K., Atrial Fibrillation Genetics Conso, Int Stroke Genetics Consortium 2018; 4 (6): e293

Abstract

We sought to assess whether genetic risk factors for atrial fibrillation (AF) can explain cardioembolic stroke risk.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.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).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.

View details for DOI 10.1212/NXG.0000000000000293

View details for Web of Science ID 000455099800017

View details for PubMedID 30584597

View details for PubMedCentralID PMC6283455