ArticleCirculation research2011
Identification of cis- and trans-acting genetic variants explaining up to half the variation in circulating vascular endothelial growth factor levels.
Article in Circulation research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 3 of them syntheses that pooled it.
What it found
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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
50 citing papers in PubMed, 3 syntheses or guidelines pooled it, 87 citations in OpenAlex.
- Genome-wide meta-analyses identifies novel taxane-induced peripheral neuropathy-associated loci.Pharmacogenetics and genomics · 2018Pooled it
- International Genome-Wide Association Study Consortium Identifies Novel Loci Associated With Blood Pressure in Children and Adolescents.Circulation. Cardiovascular genetics · 2016Pooled it
- Six Novel Loci Associated with Circulating VEGF Levels Identified by a Meta-analysis of Genome-Wide Association Studies.PLoS genetics · 2016Pooled it
- The impacts of Crocin on serum cytokines concentrations in participants with metabolic syndrome: a double-blind randomized clinical trial study.Scientific reports · 2025Trial
- New perspectives on VEGF signalling in Alzheimer's disease.Brain pathology (Zurich, Switzerland) · 2026Review
- Genetic survey of biomarkers at early and mid-pregnancy identifies pregnancy-specialized immune regulation.PLoS genetics · 2026Article
- The association of VEGF-A associated gene polymorphisms with obesity and markers of metabolic syndrome in a black South African population.BMC research notes · 2026Article
- FivePharmacogenomics and personalized medicine · 2026Article
- Polymorphisms inBiomedicines · 2025Review
- Molecular Signatures Related to Inflammation and Angiogenesis in Patients with Lower Extremity Artery Disease, Abdominal Aortic Aneurysm, and Varicose Veins: Shared and Distinct Pathways.International journal of molecular sciences · 2025Article
- VEGF-A cis-located SNPs on human chromosome 6 associated with VEGF-A plasma levels and survival in a coronary disease cohort.BMC cardiovascular disorders · 2025Article
- Vascular endothelial growth factor: a key factor in the onset and treatment of depression.Frontiers in cellular neuroscience · 2025Review
- Common variation in a long non-coding RNA gene modulates variation of circulating TGF-β2 levels in metastatic colorectal cancer patients (Alliance).BMC genomics · 2024Article
- Thrombogenesis-associated genetic determinants as predictors of thromboembolism and prognosis in cervical cancer.Scientific reports · 2023Article
- Associations of VEGF-A-Related Variants with Adolescent Cardiometabolic and Dietary Parameters.Nutrients · 2023Article
- VEGF-A related SNPs: a cardiovascular context.Frontiers in cardiovascular medicine · 2023Review
- The Association between Single Nucleotide Polymorphisms, including miR-499a Genetic Variants, and Dyslipidemia in Subjects Treated with Pharmacological or Phytochemical Lipid-Lowering Agents.International journal of molecular sciences · 2022Article
- Article
- Genetic Regulation of Cytokine Response in Patients with Acute Community-Acquired Pneumonia.Genes · 2022Article
- Article
Corrections and comments
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Authors and funding
23 authors at 6 institutions in 3 countries.
Funding
Abstract
rationaleVascular endothelial growth factor (VEGF) affects angiogenesis, atherosclerosis, and cancer. Although the heritability of circulating VEGF levels is high, little is known about its genetic underpinnings.
objectiveOur aim was to identify genetic variants associated with circulating VEGF levels, using an unbiased genome-wide approach, and to explore their functional significance with gene expression and pathway analysis. METHODS AND
resultsWe undertook a genome-wide association study of serum VEGF levels in 3527 participants of the Framingham Heart Study, with preplanned replication in 1727 participants from 2 independent samples, the STANISLAS Family Study and the Prospective Investigation of the Vasculature in Uppsala Seniors study. One hundred forty single nucleotide polymorphism (SNPs) reached genome-wide significance (P<5×10(-8)). We found evidence of replication for the most significant associations in both replication datasets. In a conditional genome-wide association study, 4 SNPs mapping to 3 chromosomal regions were independently associated with circulating VEGF levels: rs6921438 and rs4416670 (6p21.1, P=6.11×10(-506) and P=1.47×10(-12)), rs6993770 (8q23.1, P=2.50×10(-16)), and rs10738760 (9p24.2, P=1.96×10(-34)). A genetic score including these 4 SNPs explained 48% of the heritability of serum VEGF levels. Six of the SNPs that reached genome-wide significance in the genome-wide association study were significantly associated with VEGF messenger RNA levels in peripheral blood mononuclear cells. Ingenuity pathway analyses showed found plausible biological links between VEGF and 2 novel genes in these loci (ZFPM2 and VLDLR).
conclusionsGenetic variants explaining up to half the heritability of serum VEGF levels were identified. These new insights provide important clues to the pathways regulating circulating VEGF levels.
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Registered trials
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