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Coding variants in RPL3L and MYZAP increase risk of atrial fibrillation
Thorolfsdottir, Rosa B. Sveinbjornsson, Gardar Sulem, Patrick Nielsen, Jonas B. Jonsson, Stefan Halldorson, Gisli H. Melsted, Pall Ivarsdottir, Erna V. Davidsson, Olafur B. Kristjansson, Ragnar P.
Thorolfsdottir, Rosa B.
Sveinbjornsson, Gardar
Sulem, Patrick
Nielsen, Jonas B.
Jonsson, Stefan
Halldorson, Gisli H.
Melsted, Pall
Ivarsdottir, Erna V.
Davidsson, Olafur B.
Kristjansson, Ragnar P.
Author
Thorolfsdottir, Rosa B.
Sveinbjornsson, Gardar
Sulem, Patrick
Nielsen, Jonas B.
Jonsson, Stefan
Halldorson, 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
Tragante, Vinicius
Holmen, Oddgeir L.
Asselbergs, Folkert W.
Roden, Dan M.
Darbar, Dawood
Pedersen, Terje R.
Sabatine, Marc S.
Willer, Cristen J.
Loechen, Maja-Lisa
Halldorsson, Bjarni V.
Jonsdottir, Ingileif
Hveem, Kristian
Arnar, David O.
Thorsteinsdottir, Unnur
Gudbjartsson, Daniel F.
Holm, Hilma
Stefansson, Kari
Sveinbjornsson, Gardar
Sulem, Patrick
Nielsen, Jonas B.
Jonsson, Stefan
Halldorson, 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
Tragante, Vinicius
Holmen, Oddgeir L.
Asselbergs, Folkert W.
Roden, Dan M.
Darbar, Dawood
Pedersen, Terje R.
Sabatine, Marc S.
Willer, Cristen J.
Loechen, Maja-Lisa
Halldorsson, Bjarni V.
Jonsdottir, Ingileif
Hveem, Kristian
Arnar, David O.
Thorsteinsdottir, Unnur
Gudbjartsson, Daniel F.
Holm, Hilma
Stefansson, Kari
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.
Keywords
Date
2018
Type
Journal article
Journal
Communications Biology
Book
Volume
1
Issue
68
Page Range
1-9
Article Number
ACU Department
Collections
Relation URI
Source URL
Event URL
Open Access Status
Open access
License
CC BY 4.0
File Access
Open