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

Overview of attention for article published in BMC Proceedings, October 2016
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Title
Association of polymorphisms in the aldosterone-regulated sodium reabsorption pathway with blood pressure among Hispanics
Published in
BMC Proceedings, October 2016
DOI 10.1186/s12919-016-0054-5
Pubmed ID
Authors

Bamidele O. Tayo, Bamidele O. Tayo, Liping Tong, Richard S. Cooper

Abstract

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. 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. 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 <0.05) after multiple testing corrections for the number of genes. Similarly, the pathway-based 2-locus epistasis analysis indicated significant interactions between INSR and PRKCG for SBP and MAP; INS and PIK3R2 for DBP; PIK3CD and ATP1B2 for hypertension in the real data set. We also observed significant within-gene interactions in INSR for SBP, DBP, and hypertension in the simulated data set. The findings from this study show that pathway-based analytical approach targeting known biological pathways can be useful in identification of disease-associated variants that are otherwise undetectable by GWAS. The approach takes advantage of the assumption of nonindependence of variants within and across pathway genes which leads to reduced penalty of multiple testing and thus less-stringent statistical significance threshold.

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Mendeley readers

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Geographical breakdown

Country Count As %
Unknown 3 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 1 33%
Student > Postgraduate 1 33%
Unknown 1 33%
Readers by discipline Count As %
Agricultural and Biological Sciences 1 33%
Social Sciences 1 33%
Unknown 1 33%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 21 December 2016.
All research outputs
#15,404,272
of 22,914,829 outputs
Outputs from BMC Proceedings
#211
of 375 outputs
Outputs of similar age
#199,054
of 316,354 outputs
Outputs of similar age from BMC Proceedings
#3
of 6 outputs
Altmetric has tracked 22,914,829 research outputs across all sources so far. This one is in the 22nd percentile – i.e., 22% of other outputs scored the same or lower than it.
So far Altmetric has tracked 375 research outputs from this source. They receive a mean Attention Score of 4.0. This one is in the 31st percentile – i.e., 31% of its peers scored the same or lower than it.
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