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Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization
- Source :
- Nature Genetics, 46(8), 826-36. Nature Publishing Group, Nature Genetics, Vol. 46, No 8 (2014) pp. 826-836, Nature Genetics, 46(8), 826-836. Nature Publishing Group, Nature genetics, 46(8), 826-836. Nature Publishing Group, Nature genetics
- Publication Year :
- 2014
-
Abstract
- 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 similar to 8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD.
- Subjects :
- Male
Candidate gene
Myocardium/metabolism
LOCI
Medizin
Heart electrophysiology
Genome-wide association study
Arrhythmias
Bioinformatics
Medical and Health Sciences
Heart Ventricle
Sudden cardiac death
Electrocardiography
PR INTERVAL
Arrhythmias, Cardiac/genetics
Death, Sudden, Cardiac/etiology
Genetics
ddc:616
Cardiac electrophysiology
Adult
Aged
Arrhythmias, Cardiac
Calcium Signaling
Death, Sudden, Cardiac
Female
Genetic Predisposition to Disease
Genome-Wide Association Study
Genotype
Heart Ventricles
Humans
Long QT Syndrome
Middle Aged
Myocardium
Polymorphism, Single Nucleotide
COMMON VARIANTS
Heart Ventricles/metabolism
Single Nucleotide
Long QT Syndrome/genetics
CHRONIC HEART-FAILURE
Death
Heart ventricle arrhythmia
genetic association study
gene
SNP
heart
Genome-Wide Association Study/methods
Long QT syndrome
QRS DURATION
Cardiac
Cardiac/etiology
Human
QT interval
congenital, hereditary, and neonatal diseases and abnormalities
Electrocardiography/methods
TRPM7
BIO/18 - GENETICA
Cardiac/genetics
Biology
Article
sudden cardiac death
QRS complex
CARDIAC REPOLARIZATION
medicine
Repolarization
cardiovascular diseases
GENOME-WIDE ASSOCIATION
Polymorphism
MED/01 - STATISTICA MEDICA
calcium
ta1184
Calcium signaling
Calcium Signaling/genetics
MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE
ta3121
Cardiovascular risk
medicine.disease
SARCOPLASMIC-RETICULUM
Sudden
MODEL
Genetic association
myocardial repolarization
Genetic variability
Gene expression
Clinical Medicine
genetic
Controlled study
Subjects
Details
- Language :
- English
- ISSN :
- 10614036 and 15461718
- Volume :
- 46
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Nature Genetics
- Accession number :
- edsair.doi.dedup.....d931ed1c57a44ecc1929073f11e6ccfe