BDNF rs6265: Understanding the Val66Met Genetic Variant
The rs6265 variant, commonly known as Val66Met, is a single nucleotide polymorphism located in the BDNF gene. It is widely studied for its potential influence on the secretion of brain-derived neurotrophic factor, a protein essential for neuronal health, and its debated associations with memory and stress response.
What each genotype means
Val/Val genotype
This genotype represents the common Val/Val form of the BDNF protein, which is associated with typical activity-dependent secretion of brain-derived neurotrophic factor. Research suggests this form may support standard levels of neuroplasticity, though individual cognitive outcomes are influenced by a complex interplay of genetics, environment, and lifestyle factors.
This is the most common genotype globally, though frequencies vary significantly by ancestry.
Val/Met genotype
Carrying one copy of the Met allele (Val/Met) is associated with reduced activity-dependent secretion of the BDNF protein compared to the Val/Val genotype. Studies have explored links between this variant and variations in memory, stress response, and susceptibility to certain neuropsychiatric conditions, though findings across different populations remain inconsistent.
This heterozygous genotype is found in a significant portion of the population, with prevalence varying by geographic and ethnic background.
Met/Met genotype
This genotype results in the Met/Met form of the BDNF protein, which is associated with the lowest levels of activity-dependent BDNF secretion among the three genotypes. While some research links this status to differences in cognitive performance or risk for specific neurological or psychiatric traits, the clinical significance is debated and results are often mixed across different studies.
This is the least common genotype for this variant in most populations.
What is the rs6265 Variant?
The rs6265 variant is a common genetic change located on chromosome 11 at position 11p13 within the BDNF gene. In this specific location, a single nucleotide substitution occurs where an adenine replaces a guanine. This change results in an amino acid substitution in the pro-region of the BDNF protein, where valine is replaced by methionine at position 66. Because of this, the variant is frequently referred to as Val66Met. This polymorphism is unique to humans and has been the subject of extensive research due to its potential to alter the activity-dependent secretion of the BDNF protein. While it is a well-documented genetic marker, its presence does not indicate a disease state, but rather a variation in the genetic code that may influence how the brain processes and releases specific neurotrophic factors.
The Role of the BDNF Gene
The BDNF gene provides instructions for making the brain-derived neurotrophic factor protein. This protein is a member of the neurotrophin family and is highly expressed in the hippocampus, a region of the brain critical for learning and memory. BDNF plays a vital role in neurogenesis, the survival of existing neurons, and the promotion of synaptic plasticity, which is the ability of synapses to strengthen or weaken over time in response to activity. By supporting these processes, BDNF is essential for maintaining healthy brain function and cognitive performance. Because of its central role in the central nervous system, researchers have long hypothesized that variations in the BDNF gene, such as rs6265, could impact how the brain adapts to environmental challenges, stress, and the natural aging process.
Research and Evidence Strength
The scientific literature regarding rs6265 is extensive but often conflicting. While early studies suggested that the Met allele might be associated with smaller hippocampal volumes and poorer memory performance, subsequent meta-analyses and larger studies have failed to consistently replicate these findings. Some research indicates that the variant may influence executive function or antidepressant response, yet other studies find no significant association with these traits in healthy populations. The evidence for a direct link between rs6265 and specific cognitive outcomes remains limited and inconsistent. Factors such as age, sex, ethnicity, and environmental interactions likely play significant roles in how this variant manifests, making it difficult to draw definitive conclusions about its impact on any individual's cognitive health or susceptibility to neuropsychiatric conditions.
What You Can Do With This Information
Genetic information regarding the rs6265 variant is primarily for educational purposes and should not be used to make medical decisions or self-diagnose. Because the scientific community has not reached a consensus on the clinical significance of this variant, it is not considered a diagnostic tool for memory disorders or psychiatric conditions. If you are interested in your genetic profile, it is important to interpret such data within the context of your overall health, lifestyle, and environment. If you have concerns about cognitive function, memory, or mental health, you should consult with a qualified healthcare professional. Furthermore, if you are curious about how genetic variants might influence your response to specific medications, always discuss this with your clinician or pharmacist, as they can provide guidance based on established clinical guidelines rather than individual genetic markers alone.
How common is this variant?
The rs6265 variant is common, with a minor allele frequency typically reported between 0.20 and 0.25 across various global populations.
Frequently asked questions
Is the BDNF Val66Met variant a cause of Alzheimer's disease?
No, the rs6265 variant is not a direct cause of Alzheimer's disease. While some studies have explored its potential role in cognitive aging, the evidence is inconsistent and it is not used as a diagnostic marker for the condition.
Does having the Met allele mean I have poor memory?
No. Scientific research has not established a definitive link between the Met allele and poor memory in healthy individuals. Cognitive performance is influenced by a complex combination of genetics, environment, and lifestyle factors.
Can I change my BDNF expression through lifestyle?
Research suggests that lifestyle factors such as physical exercise and stress management may influence brain health and neuroplasticity. However, these activities are beneficial for everyone regardless of their specific BDNF genotype.
Should I get tested for rs6265?
There is no clinical recommendation to test for the rs6265 variant. Because the results do not currently change medical management or provide clear diagnostic information, testing is generally not considered useful for individual health planning.
Sources & further reading
Educational information only, last refreshed 10/20/2026. Not medical advice — these associations describe population statistics, not individual predictions.
Curious what your genotype is for rs6265?
Upload a raw DNA file from 23andMe, AncestryDNA, MyHeritage, or FamilyTreeDNA and see this variant — plus thousands more — interpreted in your full report.
Get my report — $29Related variants in BDNF
Variant in the BDNF region linked to allergic rhinitis and allergic asthma, modulating neurotrophin signaling during allergic airway inflammation.
Associated with modest variation in body mass index (BMI) and neurocognitive phenotypes.
Variant in the BDNF antisense/intergenic region associated with habitual physical activity levels and exercise engagement in GWAS cohorts.
Downstream regulatory variant near BDNF implicated in optic nerve neuroprotection and risk of normal tension glaucoma.