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Investigating the Genetic Architecture of the PR Interval Using Clinical Phenotypes.
Mosley, Jonathan D; Shoemaker, M Benjamin; Wells, Quinn S; Darbar, Dawood; Shaffer, Christian M; Edwards, Todd L; Bastarache, Lisa; McCarty, Catherine A; Thompson, Will; Chute, Christopher G; Jarvik, Gail P; Crosslin, David R; Larson, Eric B; Kullo, Iftikhar J; Pacheco, Jennifer A; Peissig, Peggy L; Brilliant, Murray H; Linneman, James G; Witte, John S; Denny, Josh C; Roden, Dan M.
Afiliación
  • Mosley JD; From the Department of Medicine (J.D.M., M.B.S., Q.S.W., C.M.S., J.C.D., D.M.R.), Vanderbilt Epidemiology Center (T.L.E.), Department of Biomedical Informatics (L.B., J.C.D., D.M.R.), Department of Pharmacology (D.M.R.), Vanderbilt University, Nashville, TN; Division of Cardiology, University of Ill
  • Shoemaker MB; From the Department of Medicine (J.D.M., M.B.S., Q.S.W., C.M.S., J.C.D., D.M.R.), Vanderbilt Epidemiology Center (T.L.E.), Department of Biomedical Informatics (L.B., J.C.D., D.M.R.), Department of Pharmacology (D.M.R.), Vanderbilt University, Nashville, TN; Division of Cardiology, University of Ill
  • Wells QS; From the Department of Medicine (J.D.M., M.B.S., Q.S.W., C.M.S., J.C.D., D.M.R.), Vanderbilt Epidemiology Center (T.L.E.), Department of Biomedical Informatics (L.B., J.C.D., D.M.R.), Department of Pharmacology (D.M.R.), Vanderbilt University, Nashville, TN; Division of Cardiology, University of Ill
  • Darbar D; From the Department of Medicine (J.D.M., M.B.S., Q.S.W., C.M.S., J.C.D., D.M.R.), Vanderbilt Epidemiology Center (T.L.E.), Department of Biomedical Informatics (L.B., J.C.D., D.M.R.), Department of Pharmacology (D.M.R.), Vanderbilt University, Nashville, TN; Division of Cardiology, University of Ill
  • Shaffer CM; From the Department of Medicine (J.D.M., M.B.S., Q.S.W., C.M.S., J.C.D., D.M.R.), Vanderbilt Epidemiology Center (T.L.E.), Department of Biomedical Informatics (L.B., J.C.D., D.M.R.), Department of Pharmacology (D.M.R.), Vanderbilt University, Nashville, TN; Division of Cardiology, University of Ill
  • Edwards TL; From the Department of Medicine (J.D.M., M.B.S., Q.S.W., C.M.S., J.C.D., D.M.R.), Vanderbilt Epidemiology Center (T.L.E.), Department of Biomedical Informatics (L.B., J.C.D., D.M.R.), Department of Pharmacology (D.M.R.), Vanderbilt University, Nashville, TN; Division of Cardiology, University of Ill
  • Bastarache L; From the Department of Medicine (J.D.M., M.B.S., Q.S.W., C.M.S., J.C.D., D.M.R.), Vanderbilt Epidemiology Center (T.L.E.), Department of Biomedical Informatics (L.B., J.C.D., D.M.R.), Department of Pharmacology (D.M.R.), Vanderbilt University, Nashville, TN; Division of Cardiology, University of Ill
  • McCarty CA; From the Department of Medicine (J.D.M., M.B.S., Q.S.W., C.M.S., J.C.D., D.M.R.), Vanderbilt Epidemiology Center (T.L.E.), Department of Biomedical Informatics (L.B., J.C.D., D.M.R.), Department of Pharmacology (D.M.R.), Vanderbilt University, Nashville, TN; Division of Cardiology, University of Ill
  • Thompson W; From the Department of Medicine (J.D.M., M.B.S., Q.S.W., C.M.S., J.C.D., D.M.R.), Vanderbilt Epidemiology Center (T.L.E.), Department of Biomedical Informatics (L.B., J.C.D., D.M.R.), Department of Pharmacology (D.M.R.), Vanderbilt University, Nashville, TN; Division of Cardiology, University of Ill
  • Chute CG; From the Department of Medicine (J.D.M., M.B.S., Q.S.W., C.M.S., J.C.D., D.M.R.), Vanderbilt Epidemiology Center (T.L.E.), Department of Biomedical Informatics (L.B., J.C.D., D.M.R.), Department of Pharmacology (D.M.R.), Vanderbilt University, Nashville, TN; Division of Cardiology, University of Ill
  • Jarvik GP; From the Department of Medicine (J.D.M., M.B.S., Q.S.W., C.M.S., J.C.D., D.M.R.), Vanderbilt Epidemiology Center (T.L.E.), Department of Biomedical Informatics (L.B., J.C.D., D.M.R.), Department of Pharmacology (D.M.R.), Vanderbilt University, Nashville, TN; Division of Cardiology, University of Ill
  • Crosslin DR; From the Department of Medicine (J.D.M., M.B.S., Q.S.W., C.M.S., J.C.D., D.M.R.), Vanderbilt Epidemiology Center (T.L.E.), Department of Biomedical Informatics (L.B., J.C.D., D.M.R.), Department of Pharmacology (D.M.R.), Vanderbilt University, Nashville, TN; Division of Cardiology, University of Ill
  • Larson EB; From the Department of Medicine (J.D.M., M.B.S., Q.S.W., C.M.S., J.C.D., D.M.R.), Vanderbilt Epidemiology Center (T.L.E.), Department of Biomedical Informatics (L.B., J.C.D., D.M.R.), Department of Pharmacology (D.M.R.), Vanderbilt University, Nashville, TN; Division of Cardiology, University of Ill
  • Kullo IJ; From the Department of Medicine (J.D.M., M.B.S., Q.S.W., C.M.S., J.C.D., D.M.R.), Vanderbilt Epidemiology Center (T.L.E.), Department of Biomedical Informatics (L.B., J.C.D., D.M.R.), Department of Pharmacology (D.M.R.), Vanderbilt University, Nashville, TN; Division of Cardiology, University of Ill
  • Pacheco JA; From the Department of Medicine (J.D.M., M.B.S., Q.S.W., C.M.S., J.C.D., D.M.R.), Vanderbilt Epidemiology Center (T.L.E.), Department of Biomedical Informatics (L.B., J.C.D., D.M.R.), Department of Pharmacology (D.M.R.), Vanderbilt University, Nashville, TN; Division of Cardiology, University of Ill
  • Peissig PL; From the Department of Medicine (J.D.M., M.B.S., Q.S.W., C.M.S., J.C.D., D.M.R.), Vanderbilt Epidemiology Center (T.L.E.), Department of Biomedical Informatics (L.B., J.C.D., D.M.R.), Department of Pharmacology (D.M.R.), Vanderbilt University, Nashville, TN; Division of Cardiology, University of Ill
  • Brilliant MH; From the Department of Medicine (J.D.M., M.B.S., Q.S.W., C.M.S., J.C.D., D.M.R.), Vanderbilt Epidemiology Center (T.L.E.), Department of Biomedical Informatics (L.B., J.C.D., D.M.R.), Department of Pharmacology (D.M.R.), Vanderbilt University, Nashville, TN; Division of Cardiology, University of Ill
  • Linneman JG; From the Department of Medicine (J.D.M., M.B.S., Q.S.W., C.M.S., J.C.D., D.M.R.), Vanderbilt Epidemiology Center (T.L.E.), Department of Biomedical Informatics (L.B., J.C.D., D.M.R.), Department of Pharmacology (D.M.R.), Vanderbilt University, Nashville, TN; Division of Cardiology, University of Ill
  • Witte JS; From the Department of Medicine (J.D.M., M.B.S., Q.S.W., C.M.S., J.C.D., D.M.R.), Vanderbilt Epidemiology Center (T.L.E.), Department of Biomedical Informatics (L.B., J.C.D., D.M.R.), Department of Pharmacology (D.M.R.), Vanderbilt University, Nashville, TN; Division of Cardiology, University of Ill
  • Denny JC; From the Department of Medicine (J.D.M., M.B.S., Q.S.W., C.M.S., J.C.D., D.M.R.), Vanderbilt Epidemiology Center (T.L.E.), Department of Biomedical Informatics (L.B., J.C.D., D.M.R.), Department of Pharmacology (D.M.R.), Vanderbilt University, Nashville, TN; Division of Cardiology, University of Ill
  • Roden DM; From the Department of Medicine (J.D.M., M.B.S., Q.S.W., C.M.S., J.C.D., D.M.R.), Vanderbilt Epidemiology Center (T.L.E.), Department of Biomedical Informatics (L.B., J.C.D., D.M.R.), Department of Pharmacology (D.M.R.), Vanderbilt University, Nashville, TN; Division of Cardiology, University of Ill
Circ Cardiovasc Genet ; 10(2)2017 Apr.
Article en En | MEDLINE | ID: mdl-28416512
BACKGROUND: One 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 RESULTS: We 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]). CONCLUSIONS: The genetic architecture of the PR interval comprises modulators of atrial fibrillation risk and obesity.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Fibrilación Atrial / Electrocardiografía Tipo de estudio: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adolescent / Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Circ Cardiovasc Genet Asunto de la revista: ANGIOLOGIA / CARDIOLOGIA / GENETICA MEDICA Año: 2017 Tipo del documento: Article

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Fibrilación Atrial / Electrocardiografía Tipo de estudio: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adolescent / Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Circ Cardiovasc Genet Asunto de la revista: ANGIOLOGIA / CARDIOLOGIA / GENETICA MEDICA Año: 2017 Tipo del documento: Article