Several common variants modulate heart rate, PR interval and QRS duration

Hólm, Hilma; Guðbjartsson, Daníel F.; Arnar, Davíð O.; Þorleifsson, Guðmar; Þorgeirsson, Guðmundur; Stefansdottir, Hrafnhildur; Gudjonsson, Sigurjon A.; Jónasdóttir, Áslaug; Mathiesen, Ellisiv B.; Njølstad, Inger; Nyrnes, Audhild; Wilsgaard, Tom; Hald, Erin Mathiesen; Hveem, Kristian; Stoltenberg, Camilla; Løchen, Maja‐Lisa; Kong, Augustine; Þorsteinsdóttir, Unnur; Stefánsson, Kāri

doi:10.1038/ng.511

Cited by 349 publications

(373 citation statements)

References 52 publications

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“…Norwegian biobanks are increasingly contributing to a number of cutting-edge international research projects within e.g. lung cancer, type 2 diabetes, atrial fibrillation and schizophrenia and new projects are under planning (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38). Biobank Norway will, in the coming years, continue to work for higher sample quality, improved health biobanks and registries, better research and optimized integration with our international biobank partners.…”

Section: Resultsmentioning

confidence: 99%

From Biobanks for health to Biobank Norway

Stoltenberg

Budin‐Ljøsne²,

Harris³

et al. 2012

Nor J Epidemiol

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Norwegian biobanks comprise a unique resource for researchers who want to investigate pathways to the development of common and complex diseases and improve prevention and treatment. Extensive efforts have been made in Norway during the last decade to facilitate the optimised used of human biological resources stored in the country's numerous biobanks. This paper describes the steps undertaken in the "Biobanks for Health" (BioHealth) project and the newly launched national biobank infrastructure "Biobank Norway" to lay the ground for the implementation of an infrastructure, tools and expertise that facilitate the maximised use of Norwegian biobanks and increase the ability of Norwegian researchers to participate in international research.Norwegian population cohorts, biobanks and health registries are extraordinary resources for health research. The confluence of several factors, including an integrated system to identify all residents in Norway through personal identification numbers, a predominantly single payer public health care system serving the whole population, and a democracy with strong individual rights form an environment particularly favourable to the use of these resources in biomedical research. For instance, Norwegian researchers are able to follow each person from birth or immigration to emigration or death based on linked data in deidentified research files and can study health and the effects of environments and genes across the life course of generations of Norwegians. Other Nordic countries have similar research advantages, but as yet only a few other regions and countries in the world are in an equally advantageous position. However, Norwegian researchers are just beginning to exploit the opportunities their biobanks offer. This paper describes recent initiatives undertaken in Norway to facilitate and encourage the optimised use of data and samples that comprise Norwegian biobanks for health research. Particular focus is placed on the "Biobanks for health" (BioHealth) project (1) which created a coordinated platform for the largest Norwegian population-based health studies and biobanks, and was a precursor to the

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Section: Resultsmentioning

confidence: 99%

From Biobanks for health to Biobank Norway

Stoltenberg

Budin‐Ljøsne²,

Harris³

et al. 2012

Nor J Epidemiol

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“…23,24) Only SCN10A polymorphism (rs6795970) was associated with conduction abnormality in two articles. In addition, this P value (P = 9.5 × 10 -59 ) was most significant among the other significant single nucleotide polymorphisms (SNP)s. 24) As a result, we decided to analyze the rs6795970 in the SCN10A, which have been characterized and suggested to be associated with heart block in previous GWAS. Determination of the SCN10A genes genotypes: Genomic DNA was extracted from peripheral blood samples with an extraction kit (Qiagen) according to the manufacturer's protocol.…”

Section: Methodsmentioning

confidence: 99%

“…These data suggest that this polymorphism is not directly associated with the etiology of HCM in Japanese patients. Role of SCN10A polymorphisms in heart block: Various functions have been attributed to the SCN10A as shown in Tables VII, [23][24][25][26]32) VIII, 31,33) and IX. 30) The exact role of the SCN10A polymorphisms is controversial.…”

Section: Frequency Of Polymorphismsmentioning

confidence: 99%

“…22) The SCN10A gene encodes the neuronal sodium channel isoform, Na V 1.8. Several recent genome-wide association studies (GWAS) [22][23][24][25][26] have linked SCN10A to the PR interval and QRS duration, strongly suggesting some role for Na V 1.8 in cardiac electrophysiology. The allele A of the SCN10A gene polymorphism (rs6795970) was associated with increased risk of first-degree heart block, bundle-branch block, and bifascicular heart block.…”

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confidence: 99%

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Association Between Genetic Variation in the <i>SCN10A</i> Gene and Cardiac Conduction Abnormalities in Patients With Hypertrophic Cardiomyopathy

et al. 2015

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SummaryArrhythmias are associated with reduced quality of life and poor prognosis in patients with hypertrophic cardiomyopathy (HCM). Recent genome-wide association studies revealed that a nonsynonymous single nucleotide polymorphism, rs6795970, in the SCN10A gene was associated with the PR interval. We examined whether the PR prolonging allele (A allele) in the SCN10A gene may be associated with cardiac conduction abnormalities in HCM patients.We genotyped the polymorphism in 149 HCM patients. Conduction abnormalities were defined as first-degree heart block, bundle-branch block, and bifascicular heart block. Patients were divided into two groups: group A consisted of 122 patients (82%) without a conduction abnormality; and group B consisted of 27 patients (18%) with one or more cardiac conduction abnormalities. The frequency distribution of the SCN10A genotypes (G/G, G/A, and A/A) among the patients with HCM was 71%, 26%, and 3%, respectively. A cardiac conduction abnormality was documented in 9% with G/G and 40% with G/A or A/A. There was a significant difference in the genotype distribution between the two groups (P = 0.0002). In the dominant A allele model, there was a significant difference in genotypes between the two groups (P < 0.0001). In addition, the A allele remained significant after adjusting for other covariates in a multivariate model (odds ratio = 6.30 [95% confidence interval: 2.24 to 19.09], P = 0.0005).The rs6795970 in the SCN10A gene, which is reported to carry a high risk of heart block, might be associated with cardiac conduction abnormalities in HCM patients. (Int Heart J 2015; 56: 421-427)

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“…We next considered candidate SNPs identified in previous GWAS on ECG traits [4][5][6][7][19][20][21][22][23] , using both genotype and imputation data (Supplementary Table 3). After the removal of redundant SNPs from the same haplotype (r 2 > 0.2) and the exclusion of the haplotype containing rs10428132, we observed a significant enrichment in association for the remaining 54 markers (P = 5.0 × 10 −8 ; Supplementary Fig.…”

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confidence: 99%

Erratum: Common variants at SCN5A-SCN10A and HEY2 are associated with Brugada syndrome, a rare disease with high risk of sudden cardiac death

Bezzina¹,

Barc²,

Mizusawa³

et al. 2013

Nat Genet

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Brugada syndrome is a rare cardiac arrhythmia disorder, causally related to SCN5A mutations in around 20% of cases [1][2][3] . Through a genome-wide association study of 312 individuals with Brugada syndrome and 1,115 controls, we detected 2 significant association signals at the SCN10A locus (rs10428132) and near the HEY2 gene (rs9388451). Independent replication confirmed both signals (meta-analyses: rs10428132, P = 1.0 × 10 −68 ; rs9388451, P = 5.1 × 10 −17 ) and identified one additional signal in SCN5A (at 3p21; rs11708996, P = 1.0 × 10 −14 ). The cumulative effect of the three loci on disease susceptibility was unexpectedly large (P trend = 6.1 × 10 −81 ). The association signals at SCN5A-SCN10A demonstrate that genetic polymorphisms modulating cardiac conduction 4-7 can also influence susceptibility to cardiac arrhythmia. The implication of association with HEY2, supported by new evidence that Hey2 regulates cardiac electrical activity, shows that Brugada syndrome may originate from altered transcriptional programming during cardiac development 8 . Altogether, our findings indicate that common genetic variation can have a strong impact on the predisposition to rare diseases.Sudden cardiac death (SCD) is a leading cause of mortality in Western countries, with an incidence close to 1 per 1,000 individuals per year 9 . SCD results most frequently from ventricular fibrillation in the setting of coronary artery disease 10 . In 5-10% of cases, however, SCD occurs owing to rare inherited cardiac arrhythmias, which are typically associated with a distinctive electrocardiogram (ECG) pattern in the absence of identifiable

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Several common variants modulate heart rate, PR interval and QRS duration

Cited by 349 publications

References 52 publications

From Biobanks for health to Biobank Norway

From Biobanks for health to Biobank Norway

Association Between Genetic Variation in the <i>SCN10A</i> Gene and Cardiac Conduction Abnormalities in Patients With Hypertrophic Cardiomyopathy

Erratum: Common variants at SCN5A-SCN10A and HEY2 are associated with Brugada syndrome, a rare disease with high risk of sudden cardiac death

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