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 |
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Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
Format: | Article in Journal/Newspaper |
Language: | unknown |
Published: |
Nature Publishing Group
2018
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Subjects: | |
Online Access: | https://acuresearchbank.acu.edu.au/download/dfb7e1cf768392829331d50f822d66e507f4a4dfe5c0538a6c258081316e35d4/885474/OA_Thorolfsdottir_2018_Coding_variants_in_rpl3l_and_myzap.pdf https://doi.org/10.1038/s42003-018-0068-9 |
Summary: | 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. |
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