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Articles by C. Newton Cheh
Total Records ( 2 ) for C. Newton Cheh
  E. L Akylbekova , R. S Crow , W. D Johnson , S. G Buxbaum , S Njemanze , E Fox , D. F Sarpong , H. A Taylor and C. Newton Cheh
 

Background— Electrocardiographic QT interval prolongation is a risk factor for sudden cardiac death and drug-induced arrhythmia. The clinical correlates and heritability of QT interval duration in blacks have not been well studied despite their higher risk for sudden cardiac death compared with non-Hispanic whites. We sought to investigate potential correlates of the QT interval and estimate its heritability in the Jackson Heart Study.

Methods and Results— The Jackson Heart Study comprises a sample of blacks residing in Jackson, Miss, of whom 5302 individuals with data at the baseline examination were available for study. Jackson Heart Study participants on QT-altering medications, with bundle-branch block, paced rhythm, atrial fibrillation/flutter, or other arrhythmias were excluded, resulting in a sample of 4660 individuals eligible for analyses. The relation between QT and potential covariates was tested using multivariable stepwise linear regression. Heritability was estimated using Sequential Oligogenic Linkage Analysis Routine in a subset of 1297 Jackson Heart Study participants in 292 families; the remaining sample included unrelated individuals. In stepwise multivariable linear regression analysis, covariates significantly associated with QT interval duration included R-R interval, sex, QRS duration, age, serum potassium, hypertension, body mass index, coronary heart disease, diuretic use, and Sokolow-Lyon voltage (P≤0.01 for all). The heritability of QT interval duration in the age-, sex-, and R-R interval–adjusted model and in the fully adjusted model was 0.41 (SE, 0.07) and 0.40 (SE, 0.07; P<10–11 for both), respectively.

Conclusions— There is substantial heritability of adjusted QT interval in blacks, supporting the need for further investigation to identify its genetic determinants.

  C. M Albert , C. A MacRae , D. I Chasman , M VanDenburgh , J. E Buring , J. E Manson , N. R Cook and C. Newton Cheh
  Background—

Rare variants in cardiac ion channel genes are associated with sudden cardiac death in rare primary arrhythmic syndromes; however, it is unknown whether common variation in these same genes may contribute to sudden cardiac death risk at the population level.

Methods and Results—

We examined the association between 147 single nucleotide polymorphisms (SNPs) (137 tag, 5 noncoding SNPs associated with QT interval duration, and 5 nonsynonymous SNPs) in 5 cardiac ion channel genes, KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2, and sudden and/or arrhythmic death in a combined nested case-control analysis among 516 cases and 1522 matched control subjects of European ancestry enrolled in 6 prospective cohort studies. After accounting for multiple testing, 2 SNPs (rs2283222 located in intron 11 in KCNQ1 and rs11720524 located in intron 1 in SCN5A) remained significantly associated with sudden/arrhythmic death (false discovery rate=0.01 and 0.03, respectively). Each increasing copy of the major T-allele of rs2283222 or the major C-allele of rs1172052 was associated with an odds ratio of 1.36 (95% confidence interval, 1.16 to 1.60; P=0.0002) and 1.30 (95% confidence interval, 1.12 to 1.51; P=0.0005), respectively. Control for cardiovascular risk factors and/or limiting the analysis to definite sudden cardiac death did not significantly alter these relationships.

Conclusion—

In this combined analysis of 6 prospective cohort studies, 2 common intronic variants in KCNQ1 and SCN5A were associated with sudden cardiac death in individuals of European ancestry. Further study in other populations and investigation into the functional abnormalities associated with noncoding variation in these genes may lead to important insights into predisposition to lethal arrhythmias.

 
 
 
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