ArticleCirculation2018
Phenotypic Consequences of a Genetic Predisposition to Enhanced Nitric Oxide Signaling.
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Article in Circulation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.
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62citing papers in PubMed, 1 pooled it
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Who cites it
62 citing papers in PubMed, 1 synthesis or guideline pooled it, 113 citations in OpenAlex.
- Genome-wide meta-analysis identifies 3 novel loci associated with stroke.Annals of neurology · 2018Pooled it
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- Genetic variation at the coronary artery disease risk locus GUCY1A3 modifies cardiovascular disease prevention effects of aspirin.European heart journal · 2019Trial
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- Use of soluble guanylyl cyclase stimulators in heart failure therapy-a mode of action perspective.ESC heart failure · 2026Review
- Mild traumatic brain injury promotes chronic cerebrovascular inflammation and glymphatic suppression.Molecular neurodegeneration advances · 2026Article
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- Exploration of SOCS3 and HSPA1A in PANoptosis during acute myocardial infarction and chronic kidney disease.Frontiers in cellular and infection microbiology · 2026Article
- Proteomic surveys of the mouse heart unveil cardiovascular responses to nitric oxide/cGMP signaling deficiencies.Communications biology · 2025Article
- The Ever-Expanding Influence of the Endothelial Nitric Oxide Synthase.Basic & clinical pharmacology & toxicology · 2025Review
- Single nucleotide polymorphisms: Implications in the early diagnosis and targeted intervention of coronary microvascular dysfunction.Genes & diseases · 2025Review
- Endothelial cell-related genetic variants identify LDL cholesterol-sensitive individuals who derive greater benefit from aggressive lipid lowering.Nature medicine · 2025Article
- Cardiac cGMP Regulation and Therapeutic Applications.Hypertension (Dallas, Tex. : 1979) · 2025Review
- Regulation of nitric oxide generation and consumption.International journal of biological sciences · 2025Review
- Cerebrovascular Endothelial Dysfunction: Role of BACE1.Arteriosclerosis, thrombosis, and vascular biology · 2024Review
- Hypertension: Causes and Consequences of Circadian Rhythms in Blood Pressure.Circulation research · 2024Review
- Current RNA strategies in treating cardiovascular diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Review
- Nitric oxide in vascular biology: elegance in complexity.The Journal of clinical investigation · 2024Article
- The nitric oxide-soluble guanylate cyclase-cGMP pathway in pulmonary hypertension: from PDE5 to soluble guanylate cyclase.European respiratory review : an official journal of the European Respiratory Society · 2024Review
- NOS-like activity of CeOJournal of nanobiotechnology · 2024Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
26 authors at 16 institutions in 6 countries.
Connor A EmdinCenter for Genomic Medicine (C.A.E., A.V.K., D.K., P.N., S.M.Z., A.N., M.H., K.A., A.P., N.G., S.G., S.K.).
Amit V KheraCenter for Genomic Medicine (C.A.E., A.V.K., D.K., P.N., S.M.Z., A.N., M.H., K.A., A.P., N.G., S.G., S.K.).
Derek KlarinCenter for Genomic Medicine (C.A.E., A.V.K., D.K., P.N., S.M.Z., A.N., M.H., K.A., A.P., N.G., S.G., S.K.).
Pradeep NatarajanCenter for Genomic Medicine (C.A.E., A.V.K., D.K., P.N., S.M.Z., A.N., M.H., K.A., A.P., N.G., S.G., S.K.).
Seyedeh M ZekavatCenter for Genomic Medicine (C.A.E., A.V.K., D.K., P.N., S.M.Z., A.N., M.H., K.A., A.P., N.G., S.G., S.K.).
Akihiro NomuraCenter for Genomic Medicine (C.A.E., A.V.K., D.K., P.N., S.M.Z., A.N., M.H., K.A., A.P., N.G., S.G., S.K.).
Mary HaasCenter for Genomic Medicine (C.A.E., A.V.K., D.K., P.N., S.M.Z., A.N., M.H., K.A., A.P., N.G., S.G., S.K.).
Krishna AragamCenter for Genomic Medicine (C.A.E., A.V.K., D.K., P.N., S.M.Z., A.N., M.H., K.A., A.P., N.G., S.G., S.K.).
Diego ArdissinoDivision of Cardiology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy (D.A.).
James G WilsonDepartment of Physiology and Biophysics, University of Mississippi Medical Center, Jackson (J.G.W.).
Heribert SchunkertDeutsches Herzzentrum München, Technische Universität München, Deutsches Zentrum für Herz-Kreislauf-Forschung, München, Germany (H.S.).
Ruth McPhersonUniversity of Ottawa Heart Institute, Ontario, Canada (R.M.).
Hugh WatkinsWellcome Trust Centre for Human Genetics, University of Oxford, United Kingdom (H.W.).
Roberto ElosuaCardiovascular Epidemiology and Genetics, Hospital del Mar Research Institute, Barcelona, Spain (R.E).
Matthew J BownDepartment of Cardiovascular Sciences, University of Leicester, National Institute for Health Research, Leicester Biomedical Research Centre, United Kingdom (M.J.B., N.J.S.).
Nilesh J SamaniDepartment of Cardiovascular Sciences, University of Leicester, National Institute for Health Research, Leicester Biomedical Research Centre, United Kingdom (M.J.B., N.J.S.).
Usman BaberThe Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York (U.B.).
Jeanette ErdmannInstitute for Integrative and Experimental Genomics, University of Lübeck, Germany (J.E.).
Padhraig GormleyDepartment of Medicine, Cardiology Division (C.A.E., A.V.K., P.N., S.M.Z., A.N., P.G., A.P., M.H., K.A., S.K.).
Aarno PalotieCenter for Genomic Medicine (C.A.E., A.V.K., D.K., P.N., S.M.Z., A.N., M.H., K.A., A.P., N.G., S.G., S.K.).
Nathan O StitzielDepartments of Medicine and Genetics, Cardiovascular Division, McDonnell Genome Institute, Washington University School of Medicine, St Louis, MO (N.O.S.).
Namrata GuptaCenter for Genomic Medicine (C.A.E., A.V.K., D.K., P.N., S.M.Z., A.N., M.H., K.A., A.P., N.G., S.G., S.K.).
John DaneshDepartment of Public Health and Primary Care, Cardiovascular Epidemiology Unit, University of Cambridge, United Kingdom (J.D.).
Danish SaleheenDepartment of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA (D.S.).
Stacey GabrielCenter for Genomic Medicine (C.A.E., A.V.K., D.K., P.N., S.M.Z., A.N., M.H., K.A., A.P., N.G., S.G., S.K.).
Sekar KathiresanCenter for Genomic Medicine (C.A.E., A.V.K., D.K., P.N., S.M.Z., A.N., M.H., K.A., A.P., N.G., S.G., S.K.) skathiresan1@mgh.harvard.edu.
Center for Genomic Science · ITBroad Institute · USMassachusetts General Hospital · USUniversity of Leicester · GBCentre for Human Genetics · GBGerman Centre for Cardiovascular Research · DEHarvard University · USIcahn School of Medicine at Mount Sinai · USJames S. McDonnell Foundation · USNational Institute for Health Research · GBOspedale di Parma · ITUniversitat de Vic - Universitat Central de Catalunya · ESUniversity of Lübeck · DEUniversity of Mississippi Medical Center · USUniversity of Ottawa · CAUniversity of Pennsylvania · US
Funding
Large Scale Sequencing and Analysis of GenomesU54HG003067 · NHGRI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI GABRIEL, STACEY, LANDER, ERIC S · 2004 to 2015
$568.6MTracking and Evaluation CoreU54GM115428 · NIGMS · UNIVERSITY OF MISSISSIPPI MED CTR · PI MASON, SARAH · 2016 to 2025
$38.2MNorthwest Genomics CenterRC2HL102926 · NHLBI · UNIVERSITY OF WASHINGTON · PI GREEN, PHILIP P, NICKERSON, DEBORAH A · 2009 to 2009
$11.0MComprehensive Sequencing and Analysis of Variation in NHLBI CohortsRC2HL102925 · NHLBI · BROAD INSTITUTE, INC. · PI ALTSHULER, DAVID, GABRIEL, STACEY · 2009 to 2009
$10.2MHarvard Clinical and Translational Science CenterKL2TR001100 · NCATS · HARVARD MEDICAL SCHOOL · PI NADLER, LEE MARSHALL · 2013 to 2017
$8.5MUsing genetic variation to study biology of blood lipids & coronary heart diseaseR01HL127564 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Pradeep Natarajan, Gina Marie Peloso · 2015 to 2026
$7.3MANGPTL3 DEFICIENCY AND ATHEROSCLEROSIS IN HUMANSR01HL131961 · NHLBI · WASHINGTON UNIVERSITY · PI STITZIEL, NATHAN OLIVER · 2016 to 2020
$3.2MARRA - NHLBI Lung Cohorts Sequencing ProjectRC2HL102923 · NHLBI · UNIVERSITY OF WASHINGTON · PI BAMSHAD, MICHAEL JOSEPH, BARNES, KATHLEEN C · 2009 to 2009
$2.6MWHI Sequencing Project (WHISP)RC2HL102924 · NHLBI · OHIO STATE UNIVERSITY · PI CARLSON, CHRISTOPHER S, JACKSON, REBECCA D · 2009 to 2009
$2.1MHuman Exome Sequencing in Six Well-Phenotyped NHLBI CohortsRC2HL103010 · NHLBI · UNIVERSITY OF VIRGINIA · PI RICH, STEPHEN S. · 2009 to 2009
$817kRare coding variation and risk for myocardial infarctionK08HL114642 · NHLBI · WASHINGTON UNIVERSITY · PI STITZIEL, NATHAN OLIVER · 2012 to 2016
$703kBritish Heart Foundation CS/14/2/30841Medical Research Council MC_QA137853NCATS NIH HHS KL2 TR001100NHGRI NIH HHS U54 HG003067NHLBI NIH HHS HHSN268201300046CNHLBI NIH HHS HHSN268201300047CNHLBI NIH HHS HHSN268201300048CNHLBI NIH HHS HHSN268201300049CNHLBI NIH HHS HHSN268201300050CNHLBI NIH HHS K08 HL114642NHLBI NIH HHS R01 HL127564NHLBI NIH HHS R01 HL131961NHLBI NIH HHS RC2 HL102923NHLBI NIH HHS RC2 HL102924NHLBI NIH HHS RC2 HL102925NHLBI NIH HHS RC2 HL102926NHLBI NIH HHS RC2 HL103010NIGMS NIH HHS U54 GM115428
Abstract
backgroundNitric oxide signaling plays a key role in the regulation of vascular tone and platelet activation. Here, we seek to understand the impact of a genetic predisposition to enhanced nitric oxide signaling on risk for cardiovascular diseases, thus informing the potential utility of pharmacological stimulation of the nitric oxide pathway as a therapeutic strategy.
methodsWe analyzed the association of common and rare genetic variants in 2 genes that mediate nitric oxide signaling (Nitric Oxide Synthase 3 [
resultsA genetic predisposition to enhanced nitric oxide signaling was associated with reduced risks of coronary heart disease (odds ratio, 0.37; 95% confidence interval [CI], 0.31-0.45;
conclusionsA genetic predisposition to enhanced nitric oxide signaling is associated with reduced risks of coronary heart disease, peripheral arterial disease, and stroke. Pharmacological stimulation of nitric oxide signaling may prove useful in the prevention or treatment of cardiovascular disease.
Indexed as
MutationPolymorphism, Single NucleotideBlood PressureCoronary DiseaseGenetic Association StudiesGenetic Predisposition to DiseaseHumansNitric OxideNitric Oxide Synthase Type IIIPeripheral Arterial DiseasePhenotypeProtective FactorsRisk FactorsSignal TransductionSoluble Guanylyl CyclaseStrokeGUCY1A1 protein, humanNitric OxideNitric Oxide Synthase Type IIINOS3 protein, humanSoluble Guanylyl Cyclasecardiovascular diseasegeneticsnitric oxidenitric oxide synthase
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