Genome-Wide Association Approach Identified Novel Genetic Predictors of Heart Rate Response to β-Blockers

Journal of the American Heart Association
Mohamed H ShahinJulie A Johnson

Abstract

For many indications, the negative chronotropic effect of β-blockers is important to their efficacy, yet the heart rate (HR) response to β-blockers varies. Herein, we sought to use a genome-wide association approach to identify novel single nucleotide polymorphisms (SNPs) associated with HR response to β-blockers. We first performed 4 genome-wide association analyses for HR response to atenolol (a β1-adrenergic receptor blocker) as: (1) monotherapy or (2) add-on therapy, in 426 whites and 273 blacks separately from the PEAR (Pharmacogenomic Evaluation of Antihypertensive Responses) study. A meta-analysis was then performed between the genome-wide association analysis performed in PEAR atenolol monotherapy and add-on therapy, in each race separately, using the inverse variance method assuming fixed effects. From this analysis, SNPs associated with HR response to atenolol at aP<1E-05 were tested for replication in whites (n=200) and blacks (n=168) treated with metoprolol (a β1-adrenergic receptor blocker). From the genome-wide association meta-analyses, SNP rs17117817 near olfactory receptor family10 subfamily-p-member1 (OR10P1), and SNP rs2364349 in sorting nexin-9 (SNX9) replicated in blacks. The combined studies meta-analysisP...Continue Reading

Associated Clinical Trials

References

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Citations

Nov 6, 2018·Rapid Communications in Mass Spectrometry : RCM·Amanda V QuaresmaRobson J C F Afonso
Oct 23, 2019·Pharmacogenomics·Marina BorroGiovanna Gentile
May 16, 2019·Journal of Clinical Pharmacology·Mohamed H ShahinJulie A Johnson
Sep 6, 2018·Genome Biology and Evolution·Ranajit Das, Priyanka Upadhyai
Oct 24, 2019·Cellular and Molecular Neurobiology·Grazia Rutigliano, Riccardo Zucchi
Mar 17, 2019·Clinical Science·Jian YangChunyu Zeng
Dec 30, 2020·Journal of the American Heart Association·Xuejing SunJingjing Cai
Sep 3, 2021·Lancet·Andreas KarwathUNKNOWN card AIc group and the Beta-blockers in Heart Failure Collaborative Group
Dec 1, 2021·The FEBS Journal·Juan HuangJian Yang

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Datasets Mentioned

BETA
GM074492

Methods Mentioned

BETA
Genotyping
GTPase

Clinical Trials Mentioned

NCT00246519
NCT01203852

Software Mentioned

METAL
PLINK
PEAR2
MaCH
Quanto
GenomeStudio
Minimac

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