ExomeChip-Wide Analysis of 95 626 Individuals Identifies 10 Novel Loci Associated With QT and JT Intervals.

Background: QT interval, measured through a standard ECG, captures the time it takes for the cardiac ventricles to depolarize and repolarize. JT interval is the component of the QT interval that reflects ventricular repolarization alone. Prolonged QT interval has been linked to higher risk of sudden cardiac arrest.

Erratum: Genetic loci associated with heart rate variability and their effects on cardiac disease risk.

This corrects the article DOI: 10.1038/ncomms15805.

Genetic loci associated with heart rate variability and their effects on cardiac disease risk.

Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755), expression quantitative trait loci (eQTLs) (influencing GNG11, RGS6 and NEO1), or are located in genes preferentially expressed in the sinoatrial node (GNG11, RGS6 and HCN4).

Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation.

Atrial fibrillation affects more than 33 million people worldwide and increases the risk of stroke, heart failure, and death. Fourteen genetic loci have been associated with atrial fibrillation in European and Asian ancestry groups. To further define the genetic basis of atrial fibrillation, we performed large-scale, trans-ancestry meta-analyses of common and rare variant association studies.

52 Genetic Loci Influencing Myocardial Mass.

Background: Myocardial mass is a key determinant of cardiac muscle function and hypertrophy. Myocardial depolarization leading to cardiac muscle contraction is reflected by the amplitude and duration of the QRS complex on the electrocardiogram (ECG). Abnormal QRS amplitude or duration reflect changes in myocardial mass and conduction, and are associated with increased risk of heart failure and death.

Associations between calcium and vitamin D supplement use as well as their serum concentrations and subclinical cardiovascular disease phenotypes.

Background: Supplementation of calcium (Ca) and vitamin D for the prevention of osteoporosis is frequently found in Western countries. Recent re-analyses of clinical trials observed a higher risk of myocardial infarction and stroke in subjects taking Ca (+vitamin D) supplements, although the underlying mechanisms are not clear.

Objective: Thus, we analyzed the associations between Ca and vitamin D supplementation as well as serum concentrations of Ca and 25-hydroxyvitamin D (25(OH)D) and subclinical cardiovascular disease (CVD) phenotypes, namely intima-media thickness, ankle-brachial-index (ABI), intermittent claudication, and atrial fibrillation (AF).

Short-term heart rate variability--influence of gender and age in healthy subjects.

In the recent years, short-term heart rate variability (HRV) describing complex variations of beat-to-beat interval series that are mainly controlled by the autonomic nervous system (ANS) has been increasingly analyzed to assess the ANS activity in different diseases and under various conditions. In contrast to long-term HRV analysis, short-term investigations (<30 min) provide a test result almost immediately. Thus, short-term HRV analysis is suitable for ambulatory care, patient monitoring and all those applications where the result is urgently needed.

Increased prevalence of cardiac autonomic dysfunction at different degrees of glucose intolerance in the general population: the KORA S4 survey.

Aims/hypothesis: Cardiac autonomic nervous dysfunction (CAND) raises the risk of mortality, but the glycaemic threshold at which it develops is unclear. We aimed to determine the prevalence of, risk factors for and impact of CAND in glucose intolerance and diabetes.

Methods: Among 1,332 eligible participants aged 55-74 years in the population-based cross-sectional KORA S4 study, 130 had known diabetes mellitus (k-DM), and the remaining 1,202 underwent an OGTT.

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization.

Directed acyclic graphs helped to identify confounding in the association of disability and electrocardiographic findings: results from the KORA-Age study.

Objectives: To examine the association between electrocardiographic (ECG) findings and disability status in older adults.

Study Design And Setting: KORA-Age, a population-based cross-sectional study of the MONICA/KORA project, a randomized sample from Southern Germany of people aged 65 years or older.

Results: A total of 534 (51.

A meta-analysis of genome-wide association studies of the electrocardiographic early repolarization pattern.

Background: The early repolarization pattern (ERP) is common and associated with risk of sudden cardiac death. ERP is heritable, and mutations have been described in syndromatic cases.

Objective: To conduct a meta-analysis of genome-wide association studies to identify common genetic variants influencing ERP.

Meta-analysis identifies six new susceptibility loci for atrial fibrillation.

Atrial fibrillation is a highly prevalent arrhythmia and a major risk factor for stroke, heart failure and death. We conducted a genome-wide association study (GWAS) in individuals of European ancestry, including 6,707 with and 52,426 without atrial fibrillation. Six new atrial fibrillation susceptibility loci were identified and replicated in an additional sample of individuals of European ancestry, including 5,381 subjects with and 10,030 subjects without atrial fibrillation (P < 5 × 10(-8)).

A large candidate gene survey identifies the KCNE1 D85N polymorphism as a possible modulator of drug-induced torsades de pointes.

Background: Drug-induced long-QT syndrome (diLQTS) is an adverse drug effect that has an important impact on drug use, development, and regulation. We tested the hypothesis that common variants in key genes controlling cardiac electric properties modify the risk of diLQTS.

Methods And Results: In a case-control setting, we included 176 patients of European descent from North America and Europe with diLQTS, defined as documented torsades de pointes during treatment with a QT-prolonging drug.

Multivariate short-term heart rate variability: a pre-diagnostic tool for screening heart disease.

This study has aimed to develop a novel pre-diagnostic tool for primary care screening of heart disease based on multivariate short-term heart rate variability (HRV) analyzed by linear (time and frequency domain) and nonlinear methods (compression entropy (CE), detrended fluctuation analysis (DFA), Poincaré plot analysis, symbolic dynamics) applied to 5-min ECG segments. Firstly, we applied HRV analysis to separate healthy subjects (REF) from heart disease patients (PAT). Then to optimize the results, we subdivided both groups according to gender: REF (♂ = 78, ♀ = 53) versus PAT (♂ = 378, ♀ = 115).

Common variants in 22 loci are associated with QRS duration and cardiac ventricular conduction.

The QRS interval, from the beginning of the Q wave to the end of the S wave on an electrocardiogram, reflects ventricular depolarization and conduction time and is a risk factor for mortality, sudden death and heart failure. We performed a genome-wide association meta-analysis in 40,407 individuals of European descent from 14 studies, with further genotyping in 7,170 additional Europeans, and we identified 22 loci associated with QRS duration (P < 5 × 10(-8)). These loci map in or near genes in pathways with established roles in ventricular conduction such as sodium channels, transcription factors and calcium-handling proteins, but also point to previously unidentified biologic processes, such as kinase inhibitors and genes related to tumorigenesis.

Lack of replication in polymorphisms reported to be associated with atrial fibrillation.

Background: Atrial fibrillation (AF) is the most common sustained arrhythmia and has a substantial heritable component. Numerous associations between single nucleotide polymorphisms (SNPs) and AF have been described, but few have been replicated.

Objective: We sought to systematically replicate SNPs that are reported to be associated with AF in two large study samples of European descent.

Independent susceptibility markers for atrial fibrillation on chromosome 4q25.

Background: Genetic variants on chromosome 4q25 are associated with atrial fibrillation (AF). We sought to determine whether there is more than 1 susceptibility signal at this locus.

Methods And Results: Thirty-four haplotype-tagging single-nucleotide polymorphisms (SNPs) at the 4q25 locus were genotyped in 790 case and 1177 control subjects from Massachusetts General Hospital and tested for association with AF.

Association of early repolarization pattern on ECG with risk of cardiac and all-cause mortality: a population-based prospective cohort study (MONICA/KORA).

Background: Early repolarization pattern (ERP) on electrocardiogram was associated with idiopathic ventricular fibrillation and sudden cardiac arrest in a case-control study and with cardiovascular mortality in a Finnish community-based sample. We sought to determine ERP prevalence and its association with cardiac and all-cause mortality in a large, prospective, population-based case-cohort study (Monitoring of Cardiovascular Diseases and Conditions [MONICA]/KORA [Cooperative Health Research in the Region of Augsburg]) comprised of individuals of Central-European descent.

Methods And Findings: Electrocardiograms of 1,945 participants aged 35-74 y, representing a source population of 6,213 individuals, were analyzed applying a case-cohort design.

Genome-wide association analysis identifies multiple loci related to resting heart rate.

Higher resting heart rate is associated with increased cardiovascular disease and mortality risk. Though heritable factors play a substantial role in population variation, little is known about specific genetic determinants. This knowledge can impact clinical care by identifying novel factors that influence pathologic heart rate states, modulate heart rate through cardiac structure and function or by improving our understanding of the physiology of heart rate regulation.

Usefulness of short-term variability of QT intervals as a predictor for electrical remodeling and proarrhythmia in patients with nonischemic heart failure.

The high incidence of sudden cardiac death in heart failure (HF) reflects electrophysiologic changes in response to myocardial failure. We previously showed that short-term variability of QT intervals (STV(QT)) identifies latent repolarization disorders in patients with drug-induced or congenital long QT syndrome. This study sought to determine (1) if STV(QT) is increased in patients with dilated cardiomyopathy (DC) and moderate congestive HF and (2) if increased STV(QT) is associated with ventricular arrhythmia in patients with HF.

Common variants in KCNN3 are associated with lone atrial fibrillation.

Atrial fibrillation (AF) is the most common sustained arrhythmia. Previous studies have identified several genetic loci associated with typical AF. We sought to identify common genetic variants underlying lone AF.

Genome-wide association study of PR interval.

The electrocardiographic PR interval (or PQ interval) reflects atrial and atrioventricular nodal conduction, disturbances of which increase risk of atrial fibrillation. We report a meta-analysis of genome-wide association studies for PR interval from seven population-based European studies in the CHARGE Consortium: AGES, ARIC, CHS, FHS, KORA, Rotterdam Study, and SardiNIA (N = 28,517). We identified nine loci associated with PR interval at P < 5 x 10(-8).

Common genetic variants in ANK2 modulate QT interval: results from the KORA study.

Background: Spatial and timely variations in QT interval, even within its normal range, may underlie susceptibility to cardiac arrhythmias and sudden cardiac death. Given its important role in cardiac electrophysiology, we hypothesized that common genetic variation in ankyrin-B gene (ANK2) might modify QT interval length.

Methods And Results: The study population consisted of 1188 participants of the World Health Organizational Multinational Monitoring of Trends and Determinants in Cardiovascular Disease (WHO MONICA) general population survey Cooperative Health Research in the Region of Augsburg (KORA S3).

Spontaneous Brugada electrocardiogram patterns are rare in the German general population: results from the KORA study.

Aims: The Brugada syndrome is a rare, potentially fatal primary cardiomyopathy. Patients are identified by symptoms and typical electrocardiogram (ECG) patterns. Prevalence of spontaneous Brugada ECG patterns in the general population is unknown.