Numerous Brugada syndrome-associated genetic variants have no effect on J-point elevation, syncope susceptibility, malignant cardiac arrhythmia, and all-cause mortality

Research output: Contribution to journalJournal articleResearchpeer-review

Jonas Ghouse, Christian T Have, Morten W Skov, Laura Andreasen, Gustav Ahlberg, Jonas B Nielsen, Tea Skaaby, Søren-Peter Olesen, Niels Grarup, Allan Linneberg, Oluf Pedersen, Henrik Vestergaard, Stig Haunsø, Jesper H Svendsen, Torben Hansen, Jørgen K Kanters, Morten S Olesen

PURPOSE: We investigated whether Brugada syndrome (BrS)-associated variants identified in the general population have an effect on J-point elevation as well as whether carriers of BrS variants were more prone to experience syncope and malignant ventricular arrhythmia and had increased mortality compared with noncarriers.

METHODS: All BrS-associated variants were identified using the Human Gene Mutation Database (HGMD). Individuals were randomly selected from a general population study using whole-exome sequencing data (n = 870) and genotype array data (n = 6,161) and screened for BrS-associated variants. Electrocardiograms (ECG) were analyzed electronically, and data on syncope, ventricular arrhythmias, and mortality were obtained from administrative health-care registries.

RESULTS: In HGMD, 382 BrS-associated genetic variants were identified. Of these, 28 variants were identified in the study cohort. None of the carriers presented with type 1 BrS ECG pattern. Mean J-point elevation in V1 and V2 were within normal guideline limits for carriers and noncarriers. There was no difference in syncope susceptibility (carriers 8/624; noncarriers 98/5,562; P = 0.51), ventricular arrhythmia (carriers 4/620; noncarriers 9/5,524; P = 0.24), or overall mortality (hazard ratio 0.93, 95% CI 0.63-1.4).

CONCLUSIONS: Our data indicate that a significant number of BrS-associated variants are not the monogenic cause of BrS.Genet Med advance online publication 06 October 2016Genetics in Medicine (2016); doi:10.1038/gim.2016.151.

Original languageEnglish
JournalGenetics In Medicine
Issue number5
Pages (from-to)521-528
Number of pages8
Publication statusPublished - May 2017

ID: 167474416