Genome-wide association analysis of common genetic variants of resistant hypertension

The Pharmacogenomics Journal
Nihal El RoubyJulie A Johnson

Abstract

Resistant hypertension (RHTN), defined as uncontrolled blood pressure (BP) ≥ 140/90 using three or more drugs or controlled BP (<140/90) using four or more drugs, is associated with adverse outcomes, including decline in kidney function. We conducted a genome-wide association analysis in 1194 White and Hispanic participants with hypertension and coronary artery disease from the INternational VErapamil-SR Trandolapril STudy-GENEtic Substudy (INVEST-GENES). Top variants associated with RHTN at p < 10-4 were tested for replication in 585 White and Hispanic participants with hypertension and subcortical strokes from the Secondary Prevention of Subcortical Strokes GENEtic Substudy (SPS3-GENES). A genetic risk score for RHTN was created by summing the risk alleles of replicated RHTN signals. rs11749255 in MSX2 was associated with RHTN in INVEST (odds ratio (OR) (95% CI) = 1.50 (1.2-1.8), p = 7.3 × 10-5) and replicated in SPS3 (OR = 2.0 (1.4-2.8), p = 4.3 × 10-5), with genome-wide significance in meta-analysis (OR = 1.60 (1.3-1.9), p = 3.8 × 10-8). Other replicated signals were in IFLTD1 and PTPRD. IFLTD1 rs6487504 was associated with RHTN in INVEST (OR = 1.90 (1.4-2.5), p = 1.1 × 10-5) and SPS3 (OR = 1.70 (1.2-2.5), p = 4 × 10-3). PT...Continue Reading

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Citations

Jan 17, 2019·Annals of the New York Academy of Sciences·George R Uhl, Maria J Martinez
May 1, 2021·International Journal of Molecular Sciences·Michal VrablikJaroslav A Hubacek
Jun 25, 2021·Journal of Internal Medicine·Kaya J OlczakPatricia B Munroe

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Methods Mentioned

BETA
transgenic

Clinical Trials Mentioned

NCT00133692
NCT00059306

Software Mentioned

SPRINT
SPS3
eMERGE
PLINK
INVEST SPS3
SAS
INVEST
GTEx
RegulomeDB
ICAPS

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