| Literature DB >> 30061737 |
Jonas B Nielsen1,2, Rosa B Thorolfsdottir3,4, Lars G Fritsche1,5,6,7, Wei Zhou1,7, Morten W Skov8, Sarah E Graham1,2, Todd J Herron9, Shane McCarthy10, Ellen M Schmidt11, Gardar Sveinbjornsson3, Ida Surakka1,2, Michael R Mathis12, Masatoshi Yamazaki13, Ryan D Crawford7, Maiken E Gabrielsen5,6, Anne Heidi Skogholt5,6, Oddgeir L Holmen5,6,14, Maoxuan Lin1,2, Brooke N Wolford1,7, Rounak Dey11, Håvard Dalen15,16,17, Patrick Sulem3, Jonathan H Chung10, Joshua D Backman10, David O Arnar3,4,18, Unnur Thorsteinsdottir3,4, Aris Baras10, Colm O'Dushlaine10, Anders G Holst8, Xiaoquan Wen11, Whitney Hornsby1, Frederick E Dewey10, Michael Boehnke11, Sachin Kheterpal12, Bhramar Mukherjee11, Seunggeun Lee11, Hyun M Kang11, Hilma Holm3, Jacob Kitzman2, Jordan A Shavit19, José Jalife1,9,20, Chad M Brummett12, Tanya M Teslovich10, David J Carey21, Daniel F Gudbjartsson3,22, Kari Stefansson3,4, Gonçalo R Abecasis23,24, Kristian Hveem25,26,27, Cristen J Willer28,29,30.
Abstract
To identify genetic variation underlying atrial fibrillation, the most common cardiac arrhythmia, we performed a genome-wide association study of >1,000,000 people, including 60,620 atrial fibrillation cases and 970,216 controls. We identified 142 independent risk variants at 111 loci and prioritized 151 functional candidate genes likely to be involved in atrial fibrillation. Many of the identified risk variants fall near genes where more deleterious mutations have been reported to cause serious heart defects in humans (GATA4, MYH6, NKX2-5, PITX2, TBX5)1, or near genes important for striated muscle function and integrity (for example, CFL2, MYH7, PKP2, RBM20, SGCG, SSPN). Pathway and functional enrichment analyses also suggested that many of the putative atrial fibrillation genes act via cardiac structural remodeling, potentially in the form of an 'atrial cardiomyopathy'2, either during fetal heart development or as a response to stress in the adult heart.Entities:
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Year: 2018 PMID： 30061737 PMCID： PMC6530775 DOI： 10.1038/s41588-018-0171-3
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330