Multi-ethnic genome-wide association study for atrial fibrillation

• Published in: Nature genetics Vol. 50; no. 9; pp. 1225 - 1233
• Main Authors: Roselli, Carolina, Chaffin, Mark D., Weng, Lu-Chen, Aeschbacher, Stefanie, Ahlberg, Gustav, Albert, Christine M., Alonso, Alvaro, Anderson, Christopher D., Arking, Dan E., Bartz, Traci M., Benjamin, Emelia J., Bihlmeyer, Nathan A., Bis, Joshua C., Bloom, Heather L., Brody, Jennifer A., Chen, Lin Y., Choi, Eue-Keun, Christophersen, Ingrid E., Conen, David, Cook, James, Damrauer, Scott M., Denny, Joshua C., Dudley, Samuel C., Esko, Tonu, Felix, Stephan B., Franco, Oscar H., Geelhoed, Bastiaan, Grewal, Raji P., Gutmann, Rebecca, Harris, Tamara B., Hofman, Albert, Huang, Jie, Huang, Paul L., Ito, Kaoru, Johnson, Renee, Kääb, Stefan, Kamatani, Yoichiro, Kastrati, Adnan, Katschnig-Winter, Petra, Kessler, Thorsten, Kirchhof, Paulus, Kleber, Marcus E., Kubo, Michiaki, Lin, Henry J., Lindgren, Cecilia M., Loos, Ruth J. F., Lu, Yingchang, Lyytikäinen, Leo-Pekka, Magnusson, Patrik K., Malik, Rainer, Mansur, Alfredo J., Marcus, Gregory M., März, Winfried, Melander, Olle, Müller-Nurasyid, Martina, Nazarian, Saman, Neumann, Benjamin, Newton-Cheh, Christopher, Nilsson, Peter, Noordam, Raymond, Oellers, Heidi, Pak, Hui-Nam, Pedersen, Nancy L., Psaty, Bruce M., Pulit, Sara L., Pullinger, Clive R., Ribasés, Marta, Rienstra, Michiel, Rosand, Jonathan, Rost, Natalia, Saba, Samir, Schramm, Katharina, Schurman, Claudia, Scott, Stuart A., Shaffer, Christian, Shah, Svati, Shalaby, Alaa A., Shim, Jaemin, Shoemaker, M. Benjamin, Sinner, Moritz F., Smith, Albert V., Smith, Blair H., Sun, Han, Tanaka, Toshihiro, Tanriverdi, Kahraman, Taylor, Kent D., Thériault, Sébastien, Trompet, Stella, Tucker, Nathan R., Tveit, Arnljot, Uitterlinden, Andre G., Van Der Harst, Pim, Van Wagoner, David R., Wang, Biqi, Wong, Jorge A., Woo, Daniel, Yoneda, Zachary T., Zeller, Tanja, Zeng, Lingyao, Lubitz, Steven A.
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.09.2018; Nature Publishing Group
• Subjects: 38; 38/91; 45; 45/43; 631/208; 692/699; Agriculture; Animal Genetics and Genomics; Atrial fibrillation; Atrial Fibrillation - ethnology; Atrial Fibrillation - genetics; Basic Medicine; Bioinformatics; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cardiac arrhythmia; Case-Control Studies; Consortia; Disease; Drug development; Ethnic factors; Ethnicity - genetics; Fibrillation; Gene expression; Gene Function; Gene mapping; Genes; Genetic aspects; Genetic Predisposition to Disease; Genetic research; Genome-wide association studies; Genome-Wide Association Study - methods; Genomes; Genomics; Heart; Human Genetics; Humans; Letter; Medical and Health Sciences; Medical Genetics and Genomics (including Gene Therapy); Medicin och hälsovetenskap; Medicinsk genetik och genomik (Här ingår: Genterapi); Medicinska och farmaceutiska grundvetenskaper; Meta-analysis; Muscle contraction; Mutation; Quantitative Trait Loci; RNA; Transcriptome
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/s41588-018-0133-9

Atrial fibrillation (AF) affects more than 33 million individuals worldwide 1 and has a complex heritability 2 . We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF. This large, multi-ethnic genome-wide association study identifies 97 loci significantly associated with atrial fibrillation. These loci are enriched for genes involved in cardiac development, electrophysiology, structure and contractile function.