Coding variants in RPL3L and MYZAP increase risk of atrial fibrillation
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 Icelan...
Published in: | Communications Biology |
---|---|
Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
Nature Research
2018
|
Subjects: | |
Online Access: | http://hdl.handle.net/11250/2595108 https://doi.org/10.1038/s42003-018-0068-9 |
id |
ftntnutrondheimi:oai:ntnuopen.ntnu.no:11250/2595108 |
---|---|
record_format |
openpolar |
spelling |
ftntnutrondheimi:oai:ntnuopen.ntnu.no:11250/2595108 2023-05-15T16:50:13+02:00 Coding variants in RPL3L and MYZAP increase risk of atrial fibrillation 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 Lingaas Asselbergs, Folkert W Roden, Dan M Darbar, Dawood Pedersen, Terje Rolf Sabatine, Marc S. Willer, Cristen J. Løchen, Maja-Lisa Halldorsson, Bjarni V Jonsdottir, Ingileif Hveem, Kristian Arnar, David O Thorsteinsdottir, Unnur Gudbjartsson, Daniel F. Holm, Hilma Stefansson, Kari 2018 http://hdl.handle.net/11250/2595108 https://doi.org/10.1038/s42003-018-0068-9 eng eng Nature Research Communications Biology. 2018, 1 . urn:issn:2399-3642 http://hdl.handle.net/11250/2595108 https://doi.org/10.1038/s42003-018-0068-9 cristin:1591807 Navngivelse 4.0 Internasjonal http://creativecommons.org/licenses/by/4.0/deed.no CC-BY 9 1 Communications Biology Journal article Peer reviewed 2018 ftntnutrondheimi https://doi.org/10.1038/s42003-018-0068-9 2019-09-17T06:54:57Z 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. publishedVersion © The Author(s) 2018. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License. Article in Journal/Newspaper Iceland NTNU Open Archive (Norwegian University of Science and Technology) Norway Communications Biology 1 1 |
institution |
Open Polar |
collection |
NTNU Open Archive (Norwegian University of Science and Technology) |
op_collection_id |
ftntnutrondheimi |
language |
English |
description |
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. publishedVersion © The Author(s) 2018. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License. |
format |
Article in Journal/Newspaper |
author |
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 Lingaas Asselbergs, Folkert W Roden, Dan M Darbar, Dawood Pedersen, Terje Rolf Sabatine, Marc S. Willer, Cristen J. Løchen, Maja-Lisa Halldorsson, Bjarni V Jonsdottir, Ingileif Hveem, Kristian Arnar, David O Thorsteinsdottir, Unnur Gudbjartsson, Daniel F. Holm, Hilma Stefansson, Kari |
spellingShingle |
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 Lingaas Asselbergs, Folkert W Roden, Dan M Darbar, Dawood Pedersen, Terje Rolf Sabatine, Marc S. Willer, Cristen J. Løchen, Maja-Lisa Halldorsson, Bjarni V Jonsdottir, Ingileif Hveem, Kristian Arnar, David O Thorsteinsdottir, Unnur Gudbjartsson, Daniel F. Holm, Hilma Stefansson, Kari Coding variants in RPL3L and MYZAP increase risk of atrial fibrillation |
author_facet |
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 Lingaas Asselbergs, Folkert W Roden, Dan M Darbar, Dawood Pedersen, Terje Rolf Sabatine, Marc S. Willer, Cristen J. Løchen, Maja-Lisa Halldorsson, Bjarni V Jonsdottir, Ingileif Hveem, Kristian Arnar, David O Thorsteinsdottir, Unnur Gudbjartsson, Daniel F. Holm, Hilma Stefansson, Kari |
author_sort |
Thorolfsdottir, Rosa B |
title |
Coding variants in RPL3L and MYZAP increase risk of atrial fibrillation |
title_short |
Coding variants in RPL3L and MYZAP increase risk of atrial fibrillation |
title_full |
Coding variants in RPL3L and MYZAP increase risk of atrial fibrillation |
title_fullStr |
Coding variants in RPL3L and MYZAP increase risk of atrial fibrillation |
title_full_unstemmed |
Coding variants in RPL3L and MYZAP increase risk of atrial fibrillation |
title_sort |
coding variants in rpl3l and myzap increase risk of atrial fibrillation |
publisher |
Nature Research |
publishDate |
2018 |
url |
http://hdl.handle.net/11250/2595108 https://doi.org/10.1038/s42003-018-0068-9 |
geographic |
Norway |
geographic_facet |
Norway |
genre |
Iceland |
genre_facet |
Iceland |
op_source |
9 1 Communications Biology |
op_relation |
Communications Biology. 2018, 1 . urn:issn:2399-3642 http://hdl.handle.net/11250/2595108 https://doi.org/10.1038/s42003-018-0068-9 cristin:1591807 |
op_rights |
Navngivelse 4.0 Internasjonal http://creativecommons.org/licenses/by/4.0/deed.no |
op_rightsnorm |
CC-BY |
op_doi |
https://doi.org/10.1038/s42003-018-0068-9 |
container_title |
Communications Biology |
container_volume |
1 |
container_issue |
1 |
_version_ |
1766040383762989056 |