What you carry at this position in your DNA and what research says about it.
Blood and Joint Health: 9/10 evidence, 54 publications.
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Sample genotype (not yours): C/C
Higher Oxygen Capacity and Increased Joint Risk
This genetic profile is linked to higher hemoglobin levels and improved oxygen transport, but also carries a slightly elevated risk of developing osteoarthritis. It is also associated with higher levels of beneficial HDL cholesterol.
What this genotype means: Higher hemoglobin and red blood cell count; Slightly increased risk of osteoarthritis; Higher HDL cholesterol levels.
Sample genotype (not yours): C/T
Moderate Oxygen Capacity and Balanced Joint Risk
This genotype represents a genetic middle ground, showing moderate hemoglobin levels and a slightly elevated risk for both osteoarthritis and insomnia. It also provides a mild boost to beneficial HDL cholesterol.
What this genotype means: Intermediate hemoglobin and red blood cell count; Slightly increased risk of osteoarthritis and insomnia; Slightly higher HDL cholesterol.
Sample genotype (not yours): T/T
Typical Joint Health and Higher Insomnia Risk
This genotype is associated with a lower risk of osteoarthritis and typical hemoglobin levels, but carries a higher susceptibility to insomnia. It is also linked to typical levels of HDL cholesterol.
What this genotype means: Typical hemoglobin and red blood cell count; Lower risk of osteoarthritis; Increased risk of insomnia.
Gene function and biological role
Gene Function: Vascular endothelial growth factor A, encoded by the VEGFA gene, is a critical signaling protein that stimulates the growth of new blood vessels [1]. This process, known as angiogenesis, is essential for tissue repair, wound healing, and embryonic development [1]. However, abnormal blood vessel growth can also fuel tumor progression and contribute to inflammatory conditions [2]. VEGFA plays a key role in maintaining the lining of blood vessels and regulating oxygen delivery throughout the body [1]. Variations in this gene can influence how much of the protein is produced, impacting cardiovascular health and joint integrity [3].
Variant Impact: The rs833061 variant is located in the promoter region of the VEGFA gene, where it directly influences how actively the gene is transcribed [4]. Often referred to as the -460C to T polymorphism, this genetic change alters the binding efficiency of transcription factors [4]. The C allele is generally associated with increased promoter activity, leading to higher circulating levels of the VEGF-A protein in some tissues [3]. These altered protein levels can affect blood cell production, joint cartilage maintenance, and blood vessel density [5]. Consequently, this single nucleotide change has wide-ranging effects on oxygen transport, joint health, and response to certain cancer therapies [1].
Key Insight: This variant acts like a genetic thermostat for blood vessel growth, balancing the benefits of higher oxygen-carrying capacity against the risks of joint wear and tear.
Location: VEGFA. Chromosome 6 · 6p21.1 · 43.8 Mb
Estimated prevalence by population
Global 20.2%; European 25.0%; African 11.6%; East Asian 7.5%; South Asian 20.1%; Americas 16.8%; Ashkenazi 21.6%; Finnish 30.5%; Middle Eastern 24.0%; Amish 52.1%.
Estimated CC genotype frequency.
Global 48.0%; European 50.0%; African 44.9%; East Asian 39.8%; South Asian 49.5%; Americas 48.4%; Ashkenazi 49.8%; Finnish 49.5%; Middle Eastern 50.0%; Amish 40.2%.
Estimated CT genotype frequency.
Global 31.9%; European 25.0%; African 43.5%; East Asian 52.6%; South Asian 30.5%; Americas 34.8%; Ashkenazi 28.6%; Finnish 20.1%; Middle Eastern 26.0%; Amish 7.8%.
Estimated TT genotype frequency.
Showing effects for C/C genotype
Cardiovascular & Metabolic
Blood Cell & Iron Traits
Hemoglobin Levels. Evidence: 9/10. Source: PMID 32888493. Higher Hemoglobin.
Lipids & Cholesterol
HDL Cholesterol. Evidence: 6/10. Source: PMID 39789286. Higher HDL.
Organ Systems
Bone, Joint & Connective Tissue Health
Osteoarthritis. Evidence: 6/10. Source: PMID 40205036. ~1.08x Higher Risk.
Neurology & Mental Health
Sleep & Circadian Rhythm
Insomnia. Evidence: 6/10. Source: PMID 35835914. Typical Risk.
Showing effects for C/T genotype
Hemoglobin Levels. Evidence: 9/10. Source: PMID 32888493. Slightly Higher.
HDL Cholesterol. Evidence: 6/10. Source: PMID 39789286. Slightly Higher HDL.
Osteoarthritis. Evidence: 6/10. Source: PMID 40205036. ~1.04x Higher Risk.
Insomnia. Evidence: 6/10. Source: PMID 35835914. Slightly Higher Risk.
Showing effects for T/T genotype
Hemoglobin Levels. Evidence: 9/10. Source: PMID 32888493. Typical Levels.
HDL Cholesterol. Evidence: 6/10. Source: PMID 39789286. Typical HDL.
Osteoarthritis. Evidence: 6/10. Source: PMID 40205036. Typical Risk.
Insomnia. Evidence: 6/10. Source: PMID 35835914. Higher Risk.
What this genotype means for the people who carry it
Sample genotype: CC (Homozygous)
Having two copies of the C allele leads to increased promoter activity of the VEGFA gene, which can elevate circulating VEGF-A levels [1]. This increase in growth factor activity is associated with higher hemoglobin levels, red blood cell counts, and hematocrit, which can enhance oxygen delivery to muscles and tissues [2]. However, the same biological pathway is linked to a slightly higher susceptibility to osteoarthritis, particularly in the hips [3]. On the positive side, this genetic profile is associated with higher levels of HDL cholesterol, which supports cardiovascular health [4]. Additionally, individuals with this genotype may show distinct survival patterns and side-effect profiles when treated with certain angiogenesis-inhibiting cancer therapies [5].
Higher hemoglobin and red blood cell count; Slightly increased risk of osteoarthritis; Higher HDL cholesterol levels.
Sample genotype: CT (Heterozygous)
Carrying one C allele and one T allele results in intermediate promoter activity and moderate levels of VEGF-A expression [1]. This balanced state translates to slightly higher hemoglobin levels and red blood cell counts compared to the T/T genotype, supporting typical oxygen transport [2]. However, the presence of the C allele still imparts a minor increase in the risk of developing osteoarthritis [3]. Simultaneously, the presence of the T allele introduces a slightly higher susceptibility to insomnia and sleep disruptions [4]. In cardiovascular health, this genotype is associated with a modest increase in beneficial HDL cholesterol [5]. It also influences how the body responds to specific chemotherapy and targeted cancer treatments [6].
Intermediate hemoglobin and red blood cell count; Slightly increased risk of osteoarthritis and insomnia; Slightly higher HDL cholesterol.
Sample genotype: TT (Homozygous)
Carrying two copies of the T allele is associated with lower promoter activity of the VEGFA gene, resulting in lower baseline VEGF-A expression [1]. This lower expression level is protective against osteoarthritis, giving individuals a lower risk of joint degeneration compared to C allele carriers [2]. However, this genotype is also linked to typical, rather than elevated, hemoglobin levels and red blood cell counts [3]. Furthermore, individuals with this profile have a significantly higher risk of experiencing insomnia and sleep difficulties [4]. In terms of cardiovascular biomarkers, this genotype is associated with typical levels of HDL cholesterol [5]. It also plays a role in determining response rates and survival outcomes for several cancer therapies [6].
Typical hemoglobin and red blood cell count; Lower risk of osteoarthritis; Increased risk of insomnia.
Variants with shared genetic architecture
rs699947 · VEGFA Gene · Chr 6 · Thyroid Cancer Risk
rs1570360 · VEGFA Gene · Chr 6 · Blood Vessel Health
rs2010963 · VEGFA Gene · Chr 6 · Heart and Eye Health
Contribution of VEGF polymorphisms to variation in VEGF serum levels in a healthy population.
Translational genomics of osteoarthritis in 1,962,069 individuals.
The Polygenic and Monogenic Basis of Blood Traits and Diseases.
A scalable variational inference approach for increased mixed-model association power.
Content updated August 2026.
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