Genome‐Wide Meta‐Analysis of Blood Pressure Response to β1‐Blockers: Results From ICAPS (International Consortium of Antihypertensive Pharmacogenomics Studies)
BackgroundThere exists a wide interindividual variability in blood pressure (BP) response to β1‐blockers. To identify the genetic determinants of this variability, we performed a pharmacogenomic genome‐wide meta‐analysis of genetic variants influencing β1‐blocker BP response.Methods and ResultsGenom...
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Wiley
2019-08-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
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| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.119.013115 |
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| author | Sonal Singh Helen R. Warren Timo P. Hiltunen Caitrin W. McDonough Nihal El Rouby Erika Salvi Zhiying Wang Tatiana Garofalidou Frej Fyhrquist Kimmo K. Kontula Valeria Glorioso Roberta Zaninello Nicola Glorioso Carl J. Pepine Patricia B. Munroe Stephan T. Turner Arlene B. Chapman Eric Boerwinkle Julie A. Johnson Yan Gong Rhonda M. Cooper‐DeHoff |
| author_facet | Sonal Singh Helen R. Warren Timo P. Hiltunen Caitrin W. McDonough Nihal El Rouby Erika Salvi Zhiying Wang Tatiana Garofalidou Frej Fyhrquist Kimmo K. Kontula Valeria Glorioso Roberta Zaninello Nicola Glorioso Carl J. Pepine Patricia B. Munroe Stephan T. Turner Arlene B. Chapman Eric Boerwinkle Julie A. Johnson Yan Gong Rhonda M. Cooper‐DeHoff |
| author_sort | Sonal Singh |
| collection | DOAJ |
| description | BackgroundThere exists a wide interindividual variability in blood pressure (BP) response to β1‐blockers. To identify the genetic determinants of this variability, we performed a pharmacogenomic genome‐wide meta‐analysis of genetic variants influencing β1‐blocker BP response.Methods and ResultsGenome‐wide association analysis for systolic BP and diastolic BP response to β1‐blockers from 5 randomized clinical trials consisting of 1254 patients with hypertension of European ancestry were combined in meta‐analysis and single nucleotide polymorphisms (SNPs) with P<10−4 were tested for replication in 2 independent randomized clinical trials of β1‐blocker–treated patients of European ancestry (n=1552). Regions harboring the replicated SNPs were validated in a β1‐blocker–treated black cohort from 2 randomized clinical trials (n=315). A missense SNP rs28404156 in BST1 was associated with systolic BP response to β1‐blockers in the discovery meta‐analysis (P=9.33×10−5, β=−3.21 mm Hg) and replicated at Bonferroni significance (P=1.85×10−4, β=−4.86 mm Hg) in the replication meta‐analysis with combined meta‐analysis approaching genome‐wide significance (P=2.18×10−7). This SNP in BST1 is in linkage disequilibrium with several SNPs with putative regulatory functions in nearby genes, including CD38, FBXL5, and FGFBP1, all of which have been implicated in BP regulation. SNPs in this genetic region were also associated with BP response in the black cohort.ConclusionsData from randomized clinical trials of 8 European ancestry and 2 black cohorts support the assumption that BST1 containing locus on chromosome 4 is associated with β1‐blocker BP response. Given the previous associations of this region with BP, this is a strong candidate region for future functional studies and potential use in precision medicine approaches for BP management and risk prediction. |
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| spelling | doaj.art-b76016c9f3e14e62a179e21bf16df0782022-12-21T23:53:12ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802019-08-0181610.1161/JAHA.119.013115Genome‐Wide Meta‐Analysis of Blood Pressure Response to β1‐Blockers: Results From ICAPS (International Consortium of Antihypertensive Pharmacogenomics Studies)Sonal Singh0Helen R. Warren1Timo P. Hiltunen2Caitrin W. McDonough3Nihal El Rouby4Erika Salvi5Zhiying Wang6Tatiana Garofalidou7Frej Fyhrquist8Kimmo K. Kontula9Valeria Glorioso10Roberta Zaninello11Nicola Glorioso12Carl J. Pepine13Patricia B. Munroe14Stephan T. Turner15Arlene B. Chapman16Eric Boerwinkle17Julie A. Johnson18Yan Gong19Rhonda M. Cooper‐DeHoff20Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine University of Florida Gainesville FLWilliam Harvey Research Institute Barts and The London School of Medicine and Dentistry Queen Mary University of London United KingdomDepartment of Medicine University of Helsinki and Helsinki University Hospital Helsinki FinlandDepartment of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine University of Florida Gainesville FLDepartment of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine University of Florida Gainesville FLNeuroalgology Unit Fondazione IRCCS Istituto Neurologico “Carlo Besta,” Milan ItalyHuman Genetics and Institute of Molecular Medicine University of Texas Health Science Center Houston TXWilliam Harvey Research Institute Barts and The London School of Medicine and Dentistry Queen Mary University of London United KingdomMinerva Foundation Institute for Medical Research Helsinki FinlandDepartment of Medicine University of Helsinki and Helsinki University Hospital Helsinki FinlandFaculty of Biostatistics University of Milano Bicocca ItalyHypertension and related diseases Centre Department of Clinical and Experimental Medicine University of Sassari ItalyHypertension and related diseases Centre Department of Clinical and Experimental Medicine University of Sassari ItalyDivision of Cardiovascular Medicine Department of Medicine University of Florida Gainesville FLWilliam Harvey Research Institute Barts and The London School of Medicine and Dentistry Queen Mary University of London United KingdomDivision of Nephrology and Hypertension Mayo Clinic Rochester MNDivision of Nephrology University of Chicago ILHuman Genetics and Institute of Molecular Medicine University of Texas Health Science Center Houston TXDepartment of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine University of Florida Gainesville FLDepartment of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine University of Florida Gainesville FLDepartment of Pharmacotherapy and Translational Research and Center for Pharmacogenomics and Precision Medicine University of Florida Gainesville FLBackgroundThere exists a wide interindividual variability in blood pressure (BP) response to β1‐blockers. To identify the genetic determinants of this variability, we performed a pharmacogenomic genome‐wide meta‐analysis of genetic variants influencing β1‐blocker BP response.Methods and ResultsGenome‐wide association analysis for systolic BP and diastolic BP response to β1‐blockers from 5 randomized clinical trials consisting of 1254 patients with hypertension of European ancestry were combined in meta‐analysis and single nucleotide polymorphisms (SNPs) with P<10−4 were tested for replication in 2 independent randomized clinical trials of β1‐blocker–treated patients of European ancestry (n=1552). Regions harboring the replicated SNPs were validated in a β1‐blocker–treated black cohort from 2 randomized clinical trials (n=315). A missense SNP rs28404156 in BST1 was associated with systolic BP response to β1‐blockers in the discovery meta‐analysis (P=9.33×10−5, β=−3.21 mm Hg) and replicated at Bonferroni significance (P=1.85×10−4, β=−4.86 mm Hg) in the replication meta‐analysis with combined meta‐analysis approaching genome‐wide significance (P=2.18×10−7). This SNP in BST1 is in linkage disequilibrium with several SNPs with putative regulatory functions in nearby genes, including CD38, FBXL5, and FGFBP1, all of which have been implicated in BP regulation. SNPs in this genetic region were also associated with BP response in the black cohort.ConclusionsData from randomized clinical trials of 8 European ancestry and 2 black cohorts support the assumption that BST1 containing locus on chromosome 4 is associated with β1‐blocker BP response. Given the previous associations of this region with BP, this is a strong candidate region for future functional studies and potential use in precision medicine approaches for BP management and risk prediction.https://www.ahajournals.org/doi/10.1161/JAHA.119.013115blood pressurehypertensionmeta‐analysispharmacogenomicsβ1‐blockerβ‐blocker |
| spellingShingle | Sonal Singh Helen R. Warren Timo P. Hiltunen Caitrin W. McDonough Nihal El Rouby Erika Salvi Zhiying Wang Tatiana Garofalidou Frej Fyhrquist Kimmo K. Kontula Valeria Glorioso Roberta Zaninello Nicola Glorioso Carl J. Pepine Patricia B. Munroe Stephan T. Turner Arlene B. Chapman Eric Boerwinkle Julie A. Johnson Yan Gong Rhonda M. Cooper‐DeHoff Genome‐Wide Meta‐Analysis of Blood Pressure Response to β1‐Blockers: Results From ICAPS (International Consortium of Antihypertensive Pharmacogenomics Studies) Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease blood pressure hypertension meta‐analysis pharmacogenomics β1‐blocker β‐blocker |
| title | Genome‐Wide Meta‐Analysis of Blood Pressure Response to β1‐Blockers: Results From ICAPS (International Consortium of Antihypertensive Pharmacogenomics Studies) |
| title_full | Genome‐Wide Meta‐Analysis of Blood Pressure Response to β1‐Blockers: Results From ICAPS (International Consortium of Antihypertensive Pharmacogenomics Studies) |
| title_fullStr | Genome‐Wide Meta‐Analysis of Blood Pressure Response to β1‐Blockers: Results From ICAPS (International Consortium of Antihypertensive Pharmacogenomics Studies) |
| title_full_unstemmed | Genome‐Wide Meta‐Analysis of Blood Pressure Response to β1‐Blockers: Results From ICAPS (International Consortium of Antihypertensive Pharmacogenomics Studies) |
| title_short | Genome‐Wide Meta‐Analysis of Blood Pressure Response to β1‐Blockers: Results From ICAPS (International Consortium of Antihypertensive Pharmacogenomics Studies) |
| title_sort | genome wide meta analysis of blood pressure response to β1 blockers results from icaps international consortium of antihypertensive pharmacogenomics studies |
| topic | blood pressure hypertension meta‐analysis pharmacogenomics β1‐blocker β‐blocker |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.119.013115 |
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