| Title: | Coding variants in RPL3L and MYZAP increase risk of atrial fibrillation |
| Journal: | Communications Biology |
| Published: | 12 Jun 2018 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/30271950/ |
| DOI: | https://doi.org/10.1038/s42003-018-0068-9 |
| URL: | https://www.nature.com/articles/s42003-018-0068-9.pdf |
Publication 8543
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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.</p>
35 Authors
- Rosa B. Thorolfsdottir
- Gardar Sveinbjornsson
- Patrick Sulem
- Jonas B. Nielsen
- Stefan Jonsson
- Gisli H. Halldorsson
- Pall Melsted
- Erna V. Ivarsdottir
- Olafur B. Davidsson
- Ragnar P. Kristjansson
- Gudmar Thorleifsson
- Anna Helgadottir
- Solveig Gretarsdottir
- Gudmundur Norddahl
- Sridharan Rajamani
- Bjarni Torfason
- Atli S. Valgardsson
- Jon T. Sverrisson
- Vinicius Tragante
- Oddgeir L. Holmen
- Folkert W. Asselbergs
- Dan M. Roden
- Dawood Darbar
- Terje R. Pedersen
- Marc S. Sabatine
- Cristen J. Willer
- Maja-Lisa Løchen
- Bjarni V. Halldorsson
- Ingileif Jonsdottir
- Kristian Hveem
- David O. Arnar
- Unnur Thorsteinsdottir
- Daniel F. Gudbjartsson
- Hilma Holm
- Kari Stefansson
1 Application
| Application ID | Title |
|---|---|
| 24711 | On the quest for tissue-specific contributions to disease |
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