Coding variants in RPL3L and MYZAP increase risk of atrial fibrillation

Research output: Contribution to journalArticle

Authors

  • Rosa B. Thorolfsdottir
  • Gardar Sveinbjornsson
  • Patrick Sulem
  • Jonas B. Nielsen
  • 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
  • Oddgeir L. Holmen
  • Folkert W. Asselbergs
  • Terje R. Pedersen
  • Cristen J. Willer
  • Maja Lisa Løchen
  • Bjarni V. Halldorsson
  • Ingileif Jonsdottir
  • Kristian Hveem
  • David O. Arnar
  • Unnur Thorsteinsdottir
  • Daniel F. Gudbjartsson
  • Hilma Holm
  • Kari Stefansson

External Institution(s)

  • deCODE Genetics
  • University of Iceland
  • University of Michigan, Ann Arbor
  • Landspitali University Hospital
  • Akureyri Regional Hospital
  • Utrecht University
  • Norwegian University of Science and Technology
  • Netherlands Heart Institute
  • University College London
  • University of Oslo
  • UiT The Arctic University of Norway
  • Reykjavík University
  • Nord-Trøndelag Hospital Trust

Details

Original languageEnglish (US)
Article number68
JournalCommunications Biology
Volume1
Issue number1
StatusPublished - Dec 1 2018
Peer-reviewedYes

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.

Citation formats

APA

Thorolfsdottir, R. B., Sveinbjornsson, G., Sulem, P., Nielsen, J. B., Jonsson, S., Halldorsson, G. H., ... Stefansson, K. (2018). Coding variants in RPL3L and MYZAP increase risk of atrial fibrillation. Communications Biology, 1(1), [68]. https://doi.org/10.1038/s42003-018-0068-9

Harvard

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, 'Coding variants in RPL3L and MYZAP increase risk of atrial fibrillation', Communications Biology, vol. 1, no. 1, 68. https://doi.org/10.1038/s42003-018-0068-9