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Brugada Syndrome-Associated Genetic Loci Are Associated With J-Point Elevation and an Increased Risk of Cardiac Arrest

Overview of attention for article published in Frontiers in Physiology, July 2018
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Title
Brugada Syndrome-Associated Genetic Loci Are Associated With J-Point Elevation and an Increased Risk of Cardiac Arrest
Published in
Frontiers in Physiology, July 2018
DOI 10.3389/fphys.2018.00894
Pubmed ID
Authors

Laura Andreasen, Jonas Ghouse, Morten W. Skov, Christian T. Have, Gustav Ahlberg, Peter V. Rasmussen, Allan Linneberg, Oluf Pedersen, Pyotr G. Platonov, Stig Haunsø, Jesper H. Svendsen, Torben Hansen, Jørgen K. Kanters, Morten S. Olesen

Abstract

Introduction: A previous genome-wide association study found three genetic loci, rs9388451, rs10428132, and rs11708996, to increase the risk of Brugada Syndrome (BrS). Since the effect of these loci in the general population is unknown, we aimed to investigate the effect on electrocardiogram (ECG) parameters and outcomes in the general population. Materials and Methods: A cohort of 6,161 individuals (median age 45 [interquartile range (IQR) 40-50] years, 49% males), with available digital ECGs, was genotyped and subsequently followed for a median period of 13 [IQR 12.6-13.4] years. Data on outcomes were collected from Danish administrative healthcare registries. Furthermore, ~400,000 persons from UK Biobank were investigated for associations between the three loci and cardiac arrest/ventricular fibrillation (VF). Results: Homozygote carriers of the C allele in rs6800541 intronic to SCN10A had a significantly larger J-point elevation (JPE) compared with wildtype carriers (11 vs. 6 μV, P < 0.001). There was an additive effect of carrying multiple BrS-associated risk alleles with an increased JPE in lead V1. None of the BrS-associated genetic loci predisposed to syncope, atrial fibrillation, or total mortality in the general Danish population. The rs9388451 genetic locus adjacent to the HEY2 gene was associated with cardiac arrest/VF in an analysis using the UK Biobank study (odds ratio = 1.13 (95% confidence interval: 1.08-1.18), P = 0.006). Conclusions: BrS-associated risk alleles increase the JPE in lead V1 in an additive manner, but was not associated with increased mortality or syncope in the general population of Denmark. However, the HEY2 risk allele increased the risk of cardiac arrest/VF in the larger population study of UK Biobank indicating an important role of this common genetic locus.

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Geographical breakdown

Country Count As %
Unknown 21 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 5 24%
Student > Master 4 19%
Researcher 2 10%
Student > Bachelor 2 10%
Professor 1 5%
Other 3 14%
Unknown 4 19%
Readers by discipline Count As %
Medicine and Dentistry 8 38%
Biochemistry, Genetics and Molecular Biology 7 33%
Computer Science 1 5%
Unknown 5 24%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 26 July 2018.
All research outputs
#20,527,576
of 23,096,849 outputs
Outputs from Frontiers in Physiology
#9,525
of 13,846 outputs
Outputs of similar age
#285,872
of 326,351 outputs
Outputs of similar age from Frontiers in Physiology
#415
of 507 outputs
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