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...
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ftucl:oai:eprints.ucl.ac.uk.OAI2:10080849 2023-12-24T10:17:51+01:00 Coding variants in RPL3L and MYZAP increase risk of atrial fibrillation Thorolfsdottir, RB Sveinbjornsson, G Sulem, P Nielsen, JB Jonsson, S Halldorsson, GH Melsted, P Ivarsdottir, EV Davidsson, OB Kristjansson, RP Thorleifsson, G Helgadottir, A Gretarsdottir, S Norddahl, G Rajamani, S Torfason, B Valgardsson, AS Sverrisson, JT Tragante, V Holmen, OL Asselbergs, FW Roden, DM Darbar, D Pedersen, TR Sabatine, MS Willer, CJ Løchen, ML Halldorsson, BV Jonsdottir, I Hveem, K Arnar, DO Thorsteinsdottir, U Gudbjartsson, DF Holm, H Stefansson, K 2018-06-12 text https://discovery.ucl.ac.uk/id/eprint/10080849/1/s42003-018-0068-9.pdf https://discovery.ucl.ac.uk/id/eprint/10080849/ eng eng https://discovery.ucl.ac.uk/id/eprint/10080849/1/s42003-018-0068-9.pdf https://discovery.ucl.ac.uk/id/eprint/10080849/ open Communications Biology , 1 (1) , Article 68. (2018) Article 2018 ftucl 2023-11-27T13:07:32Z 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. Article in Journal/Newspaper Iceland University College London: UCL Discovery Norway |
institution |
Open Polar |
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University College London: UCL Discovery |
op_collection_id |
ftucl |
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. |
format |
Article in Journal/Newspaper |
author |
Thorolfsdottir, RB Sveinbjornsson, G Sulem, P Nielsen, JB Jonsson, S Halldorsson, GH Melsted, P Ivarsdottir, EV Davidsson, OB Kristjansson, RP Thorleifsson, G Helgadottir, A Gretarsdottir, S Norddahl, G Rajamani, S Torfason, B Valgardsson, AS Sverrisson, JT Tragante, V Holmen, OL Asselbergs, FW Roden, DM Darbar, D Pedersen, TR Sabatine, MS Willer, CJ Løchen, ML Halldorsson, BV Jonsdottir, I Hveem, K Arnar, DO Thorsteinsdottir, U Gudbjartsson, DF Holm, H Stefansson, K |
spellingShingle |
Thorolfsdottir, RB Sveinbjornsson, G Sulem, P Nielsen, JB Jonsson, S Halldorsson, GH Melsted, P Ivarsdottir, EV Davidsson, OB Kristjansson, RP Thorleifsson, G Helgadottir, A Gretarsdottir, S Norddahl, G Rajamani, S Torfason, B Valgardsson, AS Sverrisson, JT Tragante, V Holmen, OL Asselbergs, FW Roden, DM Darbar, D Pedersen, TR Sabatine, MS Willer, CJ Løchen, ML Halldorsson, BV Jonsdottir, I Hveem, K Arnar, DO Thorsteinsdottir, U Gudbjartsson, DF Holm, H Stefansson, K Coding variants in RPL3L and MYZAP increase risk of atrial fibrillation |
author_facet |
Thorolfsdottir, RB Sveinbjornsson, G Sulem, P Nielsen, JB Jonsson, S Halldorsson, GH Melsted, P Ivarsdottir, EV Davidsson, OB Kristjansson, RP Thorleifsson, G Helgadottir, A Gretarsdottir, S Norddahl, G Rajamani, S Torfason, B Valgardsson, AS Sverrisson, JT Tragante, V Holmen, OL Asselbergs, FW Roden, DM Darbar, D Pedersen, TR Sabatine, MS Willer, CJ Løchen, ML Halldorsson, BV Jonsdottir, I Hveem, K Arnar, DO Thorsteinsdottir, U Gudbjartsson, DF Holm, H Stefansson, K |
author_sort |
Thorolfsdottir, RB |
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 |
publishDate |
2018 |
url |
https://discovery.ucl.ac.uk/id/eprint/10080849/1/s42003-018-0068-9.pdf https://discovery.ucl.ac.uk/id/eprint/10080849/ |
geographic |
Norway |
geographic_facet |
Norway |
genre |
Iceland |
genre_facet |
Iceland |
op_source |
Communications Biology , 1 (1) , Article 68. (2018) |
op_relation |
https://discovery.ucl.ac.uk/id/eprint/10080849/1/s42003-018-0068-9.pdf https://discovery.ucl.ac.uk/id/eprint/10080849/ |
op_rights |
open |
_version_ |
1786206251741347840 |