Pharmacogenomics study of thiazide diuretics and QT interval in multi-ethnic populations: the cohorts for heart and aging research in genomic epidemiology.
Pharmacogenomics J
; 18(2): 215-226, 2018 04.
Article
en En
| MEDLINE
| ID: mdl-28719597
ABSTRACT
Thiazide diuretics, commonly used antihypertensives, may cause QT interval (QT) prolongation, a risk factor for highly fatal and difficult to predict ventricular arrhythmias. We examined whether common single-nucleotide polymorphisms (SNPs) modified the association between thiazide use and QT or its component parts (QRS interval, JT interval) by performing ancestry-specific, trans-ethnic and cross-phenotype genome-wide analyses of European (66%), African American (15%) and Hispanic (19%) populations (N=78 199), leveraging longitudinal data, incorporating corrected standard errors to account for underestimation of interaction estimate variances and evaluating evidence for pathway enrichment. Although no loci achieved genome-wide significance (P<5 × 10-8), we found suggestive evidence (P<5 × 10-6) for SNPs modifying the thiazide-QT association at 22 loci, including ion transport loci (for example, NELL1, KCNQ3). The biologic plausibility of our suggestive results and simulations demonstrating modest power to detect interaction effects at genome-wide significant levels indicate that larger studies and innovative statistical methods are warranted in future efforts evaluating thiazide-SNP interactions.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Farmacogenética
/
Envejecimiento
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Etnicidad
/
Genómica
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Inhibidores de los Simportadores del Cloruro de Sodio
/
Frecuencia Cardíaca
Tipo de estudio:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
/
Screening_studies
Límite:
Adult
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Aged
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Aged80
/
Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Pharmacogenomics J
Asunto de la revista:
BIOLOGIA MOLECULAR
/
FARMACOLOGIA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Estados Unidos