Investigating the Genetic Architecture of the PR Interval Using Clinical Phenotypes.
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.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Fibrilación Atrial
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Electrocardiografía
Tipo de estudio:
Etiology_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Adolescent
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Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Circ Cardiovasc Genet
Asunto de la revista:
ANGIOLOGIA
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CARDIOLOGIA
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GENETICA MEDICA
Año:
2017
Tipo del documento:
Article