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- Title
Coding variants in RPL3L and MYZAP increase risk of atrial fibrillation.
- Authors
Thorolfsdottir, Rosa B.; Sveinbjornsson, Gardar; Sulem, Patrick; Nielsen, Jonas B.; Jonsson, Stefan; Halldorsson, Gisli H.; Melsted, Pall; Ivarsdottir, Erna V.; Davidsson, Olafur B.; Kristjansson, Ragnar P.; Thorleifsson, Gudmar; Helgadottir, Anna; Gretarsdottir, Solveig; Norddahl, Gudmundur; Rajamani, Sridharan; Torfason, Bjarni; Valgardsson, Atli S.; Sverrisson, Jon T.; Tragante, Vinicius; Holmen, Oddgeir L.
- Abstract
Most sequence variants identified hitherto in genome-wide association studies (GWAS) of atrial fibrillation are common, non-coding variants associated with risk through unknown mechanisms. We performed a meta-analysis of GWAS of atrial fibrillation among 29,502 cases and 767,760 controls from Iceland and the UK Biobank with follow-up in samples from Norway and the US, focusing on low-frequency coding and splice variants aiming to identify causal genes. We observe associations with one missense (OR = 1.20) and one splice-donor variant (OR = 1.50) in RPL3L, the first ribosomal gene implicated in atrial fibrillation to our knowledge. Analysis of 167 RNA samples from the right atrium reveals that the splice-donor variant in RPL3L results in exon skipping. We also observe an association with a missense variant in MYZAP (OR = 1.38), encoding a component of the intercalated discs of cardiomyocytes. Both discoveries emphasize the close relationship between the mechanical and electrical function of the heart. Rosa Thorolfsdottir et al. report a genome-wide association study of atrial fibrillation in 29,502 cases and 767,760 controls from Iceland and the UK Biobank. They identify a significant association with coding variants in RPL3L, the first ribosomal gene implicated in atrial fibrillation, and MYZAP, an intercalated disc gene.
- Subjects
ATRIAL fibrillation; HEART cells; ARRHYTHMIA; MUSCLE diseases; FIBROSIS
- Publication
Communications Biology, 2018, Vol 1, Issue 1, pN.PAG
- ISSN
2399-3642
- Publication type
Article
- DOI
10.1038/s42003-018-0068-9