Investigating the Genetic Architecture of the PR Interval Using Clinical Phenotypes.
Investigating the Genetic Architecture of the PR Interval Using Clinical Phenotypes.
复制标题
使用临床表型研究 PR 间隔的遗传结构。
DOI：
10.1161/circgenetics.116.001482
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发表时间：
2017
期刊：
影响因子：
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通讯作者：
Kullo,Iftik
中科院分区：
文献类型：
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作者：
Mosley,JonathanD;Shoemaker,MBenjamin;Wells,QuinnS;Darbar,Dawood;Shaffer,ChristianM;Edwards,ToddL;Bastarache,Lisa;McCarty,CatherineA;Thompson,Will;Chute,ChristopherG;Jarvik,GailP;Crosslin,DavidR;Larson,EricB;Kullo,Iftik
背景PR间期的一个潜在用途是作为疾病风险的生物标志物。我们假设，量化PR间期和一组临床表型的共享遗传结构将识别有助于PR变异性的遗传机制，并识别与PR变异性的遗传预测因子相关的疾病。（社区动脉粥样硬化风险; n=6731例受试者）和eMERGE网络（电子病历和基因组学; n= 12978）中的63种遗传调节疾病。我们测量了PR表型（PR间期，PR段，P波持续时间）和63种表型之间的成对遗传相关性（rG）。PR段与房颤有遗传相关性（rG=-0.88;P=0.0009）。ARIC的代谢表型分析也表明，P波与腰围有遗传相关性（rG=0.47;P=0.02）。基于645714个单核苷酸多态性的遗传预测PR间期表型与房颤相关（比值比=0.89/SD变化; 95%置信区间，0.83-0.95;P=0.0006）。PR表型之间的不同关联模式与分析结果一致，分析结果显示P波和PR段之间的遗传相关性与0无显著差异（rG=−0.03 [0.16]）。
BackgroundOne potential use for the PR interval is as a biomarker of disease risk. We hypothesized that quantifying the shared genetic architectures of the PR interval and a set of clinical phenotypes would identify genetic mechanisms contributing to PR variability and identify diseases associated with a genetic predictor of PR variability.Methods and ResultsWe used ECG measurements from the ARIC study (Atherosclerosis Risk in Communities; n=6731 subjects) and 63 genetically modulated diseases from the eMERGE network (Electronic Medical Records and Genomics; n=12 978). We measured pairwise genetic correlations (rG) between PR phenotypes (PR interval, PR segment, P-wave duration) and each of the 63 phenotypes. The PR segment was genetically correlated with atrial fibrillation (rG=−0.88;P=0.0009). An analysis of metabolic phenotypes in ARIC also showed that the P wave was genetically correlated with waist circumference (rG=0.47;P=0.02). A genetically predicted PR interval phenotype based on 645 714 single-nucleotide polymorphisms was associated with atrial fibrillation (odds ratio=0.89 per SD change; 95% confidence interval, 0.83–0.95;P=0.0006). The differing pattern of associations among the PR phenotypes is consistent with analyses that show that the genetic correlation between the P wave and PR segment was not significantly different from 0 (rG=−0.03 [0.16]).ConclusionsThe genetic architecture of the PR interval comprises modulators of atrial fibrillation risk and obesity.