Brugada Syndrome-Associated Genetic Loci Are Associated With J-Point Elevation and an Increased Risk of Cardiac Arrest
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Brugada Syndrome-Associated Genetic Loci Are Associated With J-Point Elevation and an Increased Risk of Cardiac Arrest. / Andreasen, Laura; Ghouse, Jonas; Skov, Morten W.; Have, Christian T.; Ahlberg, Gustav; Rasmussen, Peter V.; Linneberg, Allan; Pedersen, Oluf; Platonov, Pyotr G.; Haunsø, Stig; Svendsen, Jesper H.; Hansen, Torben; Kanters, Jørgen K.; Olesen, Morten S.
I: Frontiers in Physiology, Bind 9, 894, 2018, s. 1-9.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Brugada Syndrome-Associated Genetic Loci Are Associated With J-Point Elevation and an Increased Risk of Cardiac Arrest
AU - Andreasen, Laura
AU - Ghouse, Jonas
AU - Skov, Morten W.
AU - Have, Christian T.
AU - Ahlberg, Gustav
AU - Rasmussen, Peter V.
AU - Linneberg, Allan
AU - Pedersen, Oluf
AU - Platonov, Pyotr G.
AU - Haunsø, Stig
AU - Svendsen, Jesper H.
AU - Hansen, Torben
AU - Kanters, Jørgen K.
AU - Olesen, Morten S
PY - 2018
Y1 - 2018
N2 - 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.
AB - 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.
KW - Brugada Syndrome
KW - Electrocardiogram
KW - General population
KW - Mortality
KW - Single nucleotide polymorphism
KW - electrocardiogram
KW - single nucleotide polymorphism
KW - mortality
KW - general population
U2 - 10.3389/fphys.2018.00894
DO - 10.3389/fphys.2018.00894
M3 - Journal article
C2 - 30042696
VL - 9
SP - 1
EP - 9
JO - Frontiers in Physiology
JF - Frontiers in Physiology
SN - 1664-042X
M1 - 894
ER -
ID: 204296433