Journal article
Genome-wide association analysis of common genetic variants of resistant hypertension
The pharmacogenomics journal, v 19(3)
Jun 2019
PMID: 30237584
Featured in Collection : UN Sustainable Development Goals @ Drexel
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
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
) and replicated in SPS3 (OR = 2.0 (1.4-2.8), p = 4.3 × 10
), with genome-wide significance in meta-analysis (OR = 1.60 (1.3-1.9), p = 3.8 × 10
). 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
) and SPS3 (OR = 1.70 (1.2-2.5), p = 4 × 10
). PTPRD rs324498, a previously reported RHTN signal, was among the top signals in INVEST (OR = 1.60 (1.3-2.0), p = 3.4 × 10
) and replicated in SPS3 (OR = 1.60 (1.1-2.4), one-sided p = 0.005). Participants with the highest number of risk alleles were at increased risk of RHTN compared to participants with a lower number (p-trend = 1.8 × 10
). Overall, we identified and replicated associations with RHTN in the MSX2, IFLTD1, and PTPRD regions, and combined these associations to create a genetic risk score.
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Details
- Title
- Genome-wide association analysis of common genetic variants of resistant hypertension
- Creators
- Nihal El Rouby - Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, FL, USACaitrin W McDonough - Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, FL, USAYan Gong - Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, College of Pharmacy, University of Florida, Gainesville, FL, USALeslie A McClure - Department of Epidemiology and Biostatistics, Dornsife School of Public Health, Drexel University, Philadelphia, PA, USABraxton D Mitchell - Geriatric Research and Education Clinical Center, Veterans Administration Medical Center, Baltimore, MD, USARichard B Horenstein - Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, MD, USARobert L Talbert - College of Pharmacy, University of Texas at Austin, Austin, TX, USADana C Crawford - Epidemiology and Biostatistics, Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, USAMatthew A Gitzendanner - Department of Biology, University of Florida, Gainesville, FL, USAAtsushi Takahashi - RIKEN Center for Integrative Medical Sciences, Yokohama, JapanToshihiro Tanaka - RIKEN Center for Integrative Medical Sciences, Yokohama, JapanMichiaki Kubo - RIKEN Center for Integrative Medical Sciences, Yokohama, JapanCarl J Pepine - Division of Cardiovascular Medicine, Department of Medicine, University of Florida, Gainesville, FL, USARhonda M Cooper-DeHoff - Division of Cardiovascular Medicine, Department of Medicine, University of Florida, Gainesville, FL, USAOscar R Benavente - Department of Neurology, University of British Columbia, Vancouver, BC, CanadaAlan R Shuldiner - Program for Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, MD, USAJulie A Johnson - Division of Cardiovascular Medicine, Department of Medicine, University of Florida, Gainesville, FL, USA. johnson@cop.ufl.edu
- Publication Details
- The pharmacogenomics journal, v 19(3)
- Publisher
- Springer Nature; United States
- Grant note
- U01-GM074492 / NIH HHS U01 HG004608 / NHGRI NIH HHS NIH R01 HL074730 / NIH HHS U01 GM074492 / NIGMS NIH HHS 1 KL2 TR001429 / NIH HHS KL2 TR001429 / NCATS NIH HHS U01 HG006380 / NHGRI NIH HHS UL1 TR000445 / NCATS NIH HHS U01HG006378 / NIH HHS U01 HG006378 / NHGRI NIH HHS T32 HL083810 / NHLBI NIH HHS U01 HG004599 / NHGRI NIH HHS R01 HL074730 / NHLBI NIH HHS U01HG04603 / NIH HHS U01 HG004610 / NHGRI NIH HHS U01 HG006385 / NHGRI NIH HHS U01 HG006389 / NHGRI NIH HHS U01 HG006382 / NHGRI NIH HHS R01 NS073346 / NIH HHS R01 NS073346 / NINDS NIH HHS U01 HG004603 / NHGRI NIH HHS U01 HG004609 / NHGRI NIH HHS U01 HG006388 / NHGRI NIH HHS U01GM074492-05S109 / NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Epidemiology and Biostatistics
- Web of Science ID
- WOS:000474346300009
- Scopus ID
- 2-s2.0-85053779227
- Other Identifier
- 991014878275104721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Genetics & Heredity
- Pharmacology & Pharmacy