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Association of polymorphisms in the aldosterone-regulated sodium reabsorption pathway with blood pressure among Hispanics

Association of polymorphisms in the aldosterone-regulated sodium reabsorption pathway with blood pressure among Hispanics

Authors :
Bamidele O. Tayo
Liping Tong
Richard S. Cooper
Source :
BMC Proceedings
Publisher :
Springer Nature

Abstract

Background Whereas genome-wide association study (GWAS) has proven to be an important tool for discovery of variants influencing many human diseases and traits, unfortunately its performance has not been much of all-around success for some complex conditions, for example, hypertension. Because some of the existing effective pharmacotherapeutic agents act by targeting known biological pathways, pathway-based analytical approaches could lead to more success in discovery of disease-associated variants. The objective of the present study was to identify functional variants associated with blood pressure in the aldosterone-regulated sodium reabsorption pathway using the simulated and real blood pressure phenotypes provided for Genetic Analysis Workshop 19. Methods The present analysis included 1942 samples with exome sequencing data and for whom blood pressure phenotypes were available. Because only odd-numbered autosomes were available, we restricted analysis to 127 quality-controlled single-nucleotide polymorphisms from the aldosterone-regulated sodium reabsorption pathway. We performed pathway-based association analysis using appropriate regression models for single variant, haplotype and epistasis association analyses. To account for multiple comparisons, statistical significance was empirically derived by permutation procedure and Bonferroni correction. Results The topmost pathway-based association signals were observed in PRKCA gene for diastolic blood pressure (DBP), systolic blood pressure (SBP), and mean arterial pressure (MAP) in both real and simulated data. The associations remained significant (P

Details

Language :
English
ISSN :
17536561
Volume :
10
Issue :
S7
Database :
OpenAIRE
Journal :
BMC Proceedings
Accession number :
edsair.doi.dedup.....c959f15fda3327980b81a34f3370017a
Full Text :
https://doi.org/10.1186/s12919-016-0054-5