SynthesisHypertension (Dallas, Tex. : 1979)2012
Genomewide association study using a high-density single nucleotide polymorphism array and case-control design identifies a novel essential hypertension susceptibility locus in the promoter region of endothelial NO synthase.
Synthesis in Hypertension (Dallas, Tex. : 1979), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 10 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
79 citing papers in PubMed, 10 syntheses or guidelines pooled it, 156 citations in OpenAlex.
- A multiancestry polygenic risk score improves stratification in patients with hypertrophic cardiomyopathy.Nature cardiovascular research · 2026Pooled it
- Identification of risk loci for primary aldosteronism in genome-wide association studies.Nature communications · 2022Pooled it
- A multi-step genomic approach prioritized TBKBP1 gene as relevant for multiple sclerosis susceptibility.Journal of neurology · 2022Pooled it
- Pooled it
- Genome-Wide Meta-Analysis Identifies Three Novel Susceptibility Loci and Reveals Ethnic Heterogeneity of Genetic Susceptibility for IgA Nephropathy.Journal of the American Society of Nephrology : JASN · 2020Pooled it
- Resistant Hypertension: Detection, Evaluation, and Management: A Scientific Statement From the American Heart Association.Hypertension (Dallas, Tex. : 1979) · 2018Guideline
- Common variants at PVT1, ATG13-AMBRA1, AHI1 and CLEC16A are associated with selective IgA deficiency.Nature genetics · 2016Pooled it
- A comprehensive 1,000 Genomes-based genome-wide association meta-analysis of coronary artery disease.Nature genetics · 2015Pooled it
- Gene-centric meta-analysis in 87,736 individuals of European ancestry identifies multiple blood-pressure-related loci.American journal of human genetics · 2014Pooled it
- Loci influencing blood pressure identified using a cardiovascular gene-centric array.Human molecular genetics · 2013Pooled it
- TET2 and CSMD1 genes affect SBP response to hydrochlorothiazide in never-treated essential hypertensives.Journal of hypertension · 2015Trial
- Pharmacogenetic association of NOS3 variants with cardiovascular disease in patients with hypertension: the GenHAT study.PloS one · 2012Trial
- Endothelin: A Potential Universal Systemic Biomarker.Current medicinal chemistry · 2026Review
- Review
- Impact of vitamin D supplementation on cognitive impairment in elderly individuals with hypertension.Frontiers in neurology · 2025Article
- Mechanism-free repurposing of drugs for C9orf72-related ALS/FTD using large-scale genomic data.Cell genomics · 2024Article
- Genetic and functional analysis of Raynaud's syndrome implicates loci in vasculature and immunity.Cell genomics · 2024Article
- Functional polymorphisms ofFrontiers in genetics · 2024Article
- Inhibiting Intracellular αInternational journal of molecular sciences · 2023Article
- Intracranial Aneurysms and Genetics: An Extensive Overview of Genomic Variations, Underlying Molecular Dynamics, Inflammatory Indicators, and Forward-Looking Insights.Brain sciences · 2023Review
19 more citing papers are in PubMed but not listed here.
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Authors and funding
59 authors at 5 institutions in 5 countries.
Funding
Abstract
Essential hypertension is a multifactorial disorder and is the main risk factor for renal and cardiovascular complications. The research on the genetics of hypertension has been frustrated by the small predictive value of the discovered genetic variants. The HYPERGENES Project investigated associations between genetic variants and essential hypertension pursuing a 2-stage study by recruiting cases and controls from extensively characterized cohorts recruited over many years in different European regions. The discovery phase consisted of 1865 cases and 1750 controls genotyped with 1M Illumina array. Best hits were followed up in a validation panel of 1385 cases and 1246 controls that were genotyped with a custom array of 14 055 markers. We identified a new hypertension susceptibility locus (rs3918226) in the promoter region of the endothelial NO synthase gene (odds ratio: 1.54 [95% CI: 1.37-1.73]; combined P=2.58 · 10(-13)). A meta-analysis, using other in silico/de novo genotyping data for a total of 21 714 subjects, resulted in an overall odds ratio of 1.34 (95% CI: 1.25-1.44; P=1.032 · 10(-14)). The quantitative analysis on a population-based sample revealed an effect size of 1.91 (95% CI: 0.16-3.66) for systolic and 1.40 (95% CI: 0.25-2.55) for diastolic blood pressure. We identified in silico a potential binding site for ETS transcription factors directly next to rs3918226, suggesting a potential modulation of endothelial NO synthase expression. Biological evidence links endothelial NO synthase with hypertension, because it is a critical mediator of cardiovascular homeostasis and blood pressure control via vascular tone regulation. This finding supports the hypothesis that there may be a causal genetic variation at this locus.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.