Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation

Christophersen, I. E. et al. (2017) Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation. Nature Genetics, 49(6), pp. 946-952. (doi: 10.1038/ng.3843) (PMID:28416818)

Abstract

Atrial fibrillation affects more than 33 million people worldwide and increases the risk of stroke, heart failure, and death. Fourteen genetic loci have been associated with atrial fibrillation in European and Asian ancestry groups. To further define the genetic basis of atrial fibrillation, we performed large-scale, trans-ancestry meta-analyses of common and rare variant association studies. The genome-wide association studies (GWAS) included 17,931 individuals with atrial fibrillation and 115,142 referents; the exome-wide association studies (ExWAS) and rare variant association studies (RVAS) involved 22,346 cases and 132,086 referents. We identified 12 new genetic loci that exceeded genome-wide significance, implicating genes involved in cardiac electrical and structural remodeling. Our results nearly double the number of known genetic loci for atrial fibrillation, provide insights into the molecular basis of atrial fibrillation, and may facilitate the identification of new potential targets for drug discovery.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Macfarlane, Professor Peter and Ford, Professor Ian and Padmanabhan, Professor Sandosh
• Authors: Christophersen, I. E., Rienstra, M., Roselli, C., Yin, X., Geelhoed, B., Barnard, J., Lin, H., Arking, D. E., Smith, A. V., Albert, C. M., Chaffin, M., Tucker, N. R., Li, M., Klarin, D., Bihlmeyer, N. A., Low, S.-K., Weeke, P. E., Müller-Nurasyid, M., Smith, J. G., Brody, J. A., Niemeijer, M. N., Dörr, M., Trompet, S., Huffman, J., Gustafsson, S., Schurmann, C., Kleber, M. E., Lyytikäinen, L.-P., Seppälä, I., Malik, R., Horimoto, A. R.V.R., Perez, M., Sinisalo, J., Aeschbacher, S., Thériault, S., Yao, J., Radmanesh, F., Weiss, S., Teumer, A., Choi, S. H., Weng, L.-C., Clauss, S., Deo, R., Rader, D. J., Shah, S. H., Sun, A., Hopewell, J. C., Debette, S., Chauhan, G., Yang, Q., Worrall, B. B., Paré, 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. B., Padmanabhan, S., Haessler, J., Bartz, T. M., Waldenberger, M., Lichtner, P., Arendt, M., Krieger, J. E., Kähönen, 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.-D. I., Sandhu, R. K., Li, M., Boerwinkle, E., Eisele, L., Lannfelt, L., Rost, N., Anderson, C. D., 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-Heimbach, S., Almgren, P., Huang, P. L., Sotoodehnia, N., Soliman, E. Z., Uitterlinden, A. G., Hofman, A., Franco, O. H., Völker, U., Jöckel, K.-H., Sinner, M. F., Lin, H. J., Guo, X., Dichgans, M., Ingelsson, E., Kooperberg, C., Melander, O., Loos, R. J.F., Laurikka, J., Conen, D., Rosand, J., van der Harst, P., Lokki, M.-L., Kathiresan, S., Pereira, A., Jukema, J. W., Hayward, C., Rotter, J. I., März, W., Lehtimäki, T., Stricker, B. H., Chung, M. K., Felix, S. B., Gudnason, V., Alonso, A., Roden, D. M., Kääb, S., Chasman, D. I., Heckbert, S. R., Benjamin, E. J., Tanaka, T., Lunetta, K. L., Lubitz, S. A., and Ellinor, P. T.
• Subjects: R Medicine > R Medicine (General)
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre
• Journal Name: Nature Genetics
• Publisher: Nature Publishing Group
• ISSN: 1061-4036
• ISSN (Online): 1546-1718
• Published Online: 17 April 2017
• Copyright Holders: Copyright © 2017 Nature America, Inc., part of Springer Nature
• First Published: First published in Nature Genetics 49(6): 946-952
• Publisher Policy: Reproduced in accordance with the publisher copyright policy