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Common variants in myocardial ion channel genes modify the QT interval in the general population: Results from the KORA study.
Circ. Res. 96, 693-701 (2005)
Altered myocardial repolarization is one of the important substrates of ventricular tachycardia and fibrillation. The influence of rare gene variants on repolarization is evident in familial long QT syndrome. To investigate the influence of common gene variants on the QT interval we performed a linkage disequilibrium based SNP association study of four candidate genes. Using a two-step design we analyzed 174 SNPs from the KCNQ1, KCNH2, KCNE1, and KCNE2 genes in 689 individuals from the population-based KORA study and 14 SNPs with results suggestive of association in a confirmatory sample of 3277 individuals from the same survey. We detected association to a gene variant in intron 1 of the KCNQ1 gene (rs757092, +1.7 ms/allele, P=0.0002) and observed weaker association to a variant upstream of the KCNE1 gene (rs727957, +1.2 ms/allele, P=0.0051). In addition we detected association to two SNPs in the KCNH2 gene, the previously described K897T variant (rs1805123, −1.9 ms/allele, P=0.0006) and a gene variant that tags a different haplotype in the same block (rs3815459, +1.7 ms/allele, P=0.0004). The analysis of additive effects by an allelic score explained a 10.5 ms difference in corrected QT interval length between extreme score groups and 0.95% of trait variance (P<0.00005). These results confirm previous heritability studies indicating that repolarization is a complex trait with a significant heritable component and demonstrate that high-resolution SNP-mapping in large population samples can detect and fine map quantitative trait loci even if locus specific heritabilities are small.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
arrhythmia
cardiovascular genomics
ECG
quantitative trait locus
multiple locus association study
Language
english
Publication Year
2005
HGF-reported in Year
0
ISSN (print) / ISBN
0009-7330
e-ISSN
1524-4571
Journal
Circulation Research
Quellenangaben
Volume: 96,
Pages: 693-701
Publisher
Lippincott Williams & Wilkins
Reviewing status
Peer reviewed
Institute(s)
Institute of Biological and Medical Imaging (IBMI)
Institute of Health Economics and Health Care Management (IGM)
Institute of Epidemiology (EPI)
Institute of Human Genetics (IHG)
Institute of Health Economics and Health Care Management (IGM)
Institute of Epidemiology (EPI)
Institute of Human Genetics (IHG)
POF-Topic(s)
30205 - Bioengineering and Digital Health
30202 - Environmental Health
30503 - Chronic Diseases of the Lung and Allergies
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
30202 - Environmental Health
30503 - Chronic Diseases of the Lung and Allergies
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
Research field(s)
Enabling and Novel Technologies
Genetics and Epidemiology
Genetics and Epidemiology
PSP Element(s)
G-505500-003
G-505300-002
G-503900-001
G-500700-001
G-504090-001
G-505300-002
G-503900-001
G-500700-001
G-504090-001
Erfassungsdatum
2005-06-01