Mutations in RPL3L and MYZAP increase risk of atrial fibrillation
By
Rosa B. Thorolfsdottir,
Gardar Sveinbjornsson,
Patrick Sulem,
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,
Folkert W Asselbergs,
Dan M. Roden,
Dawood Darbar,
Terje R Pedersen,
Marc S Sabatine,
Maja-Lisa Løchen,
Bjarni V Halldorsson,
Ingileif Jonsdottir,
David O. Arnar,
Unnur Thorsteinsdottir,
Daniel F. Gudbjartsson,
Hilma Holm,
Kari Stefansson
Posted 21 Nov 2017
bioRxiv DOI: 10.1101/223578
We performed a meta-analysis of genome-wide association studies on atrial fibrillation (AF) among 14,710 cases and 373,897 controls from Iceland and 14,792 cases and 393,863 controls from the UK Biobank, focusing on low frequency coding and splice mutations, with follow-up in samples from Norway and the US. We observed associations with two missense (OR=1.19 for both) and one splice-donor mutation (OR=1.52) in RPL3L, encoding a ribosomal protein primarily expressed in skeletal muscle and heart. Analysis of 167 RNA samples from the right atrium revealed that the splice donor mutation in RPL3L results in exon skipping. AF is the first disease associated with RPL3L and RPL3L is the first ribosomal gene implicated in AF. This finding is consistent with tissue specialization of ribosomal function. We also found an association with a missense variant in MYZAP (OR=1.37), encoding a component of the intercalated discs of cardiomyocytes, the organelle harbouring most of the mutated proteins involved in arrhythmogenic right ventricular cardiomyopathy. Both discoveries emphasize the close relationship between the mechanical and electrical function of the heart.
Download data
- Downloaded 451 times
- Download rankings, all-time:
- Site-wide: 55,721
- In genetics: 2,645
- Year to date:
- Site-wide: 55,931
- Since beginning of last month:
- Site-wide: 68,220
Altmetric data
Downloads over time
Distribution of downloads per paper, site-wide
PanLingua
News
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!