What you carry at this position in your DNA and what research says about it.
Weight and Joint Health: 8/10 evidence, 24 publications.
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Sample genotype (not yours): A/A
Higher Risk of Obesity and Joint Issues
Having two copies of the A allele is associated with a higher average body mass index and an increased risk of developing osteoarthritis. However, it is linked to a typical response to antipsychotic medications.
What this genotype means: Higher average body mass index; Elevated risk of osteoarthritis; Typical response to antipsychotic medications.
Sample genotype (not yours): A/G
Intermediate Weight Risk and Reduced Medication Response
Carrying one copy of each allele is linked to a moderate risk of elevated body mass index and osteoarthritis. It is also associated with a poorer response to certain antipsychotic medications.
What this genotype means: Moderate risk of elevated body mass index; Slightly reduced response to antipsychotic medications; Typical physical grip strength.
Sample genotype (not yours): G/G
Lower Obesity Risk and Poorer Medication Response
Carrying two copies of the G allele is linked to a lower average body mass index, higher grip strength, and a lower risk of osteoarthritis. However, it is associated with a poorer response to antipsychotic medications.
What this genotype means: Lower average body mass index; Reduced risk of osteoarthritis; Poorer response to antipsychotic medications.
Gene function and biological role
Gene Function: Brain-derived neurotrophic factor is a critical protein that supports the survival, growth, and maintenance of neurons in the brain [1]. It plays a vital role in synaptic plasticity, which is essential for learning, memory, and cognitive function [1]. Beyond its neurological roles, this protein is heavily involved in regulating energy balance, appetite, and body weight through hypothalamic pathways [2]. Variations in this gene have been linked to a wide range of psychiatric conditions, cognitive traits, and metabolic outcomes [3].
Variant Impact: Located within an intron of the BDNF gene, this genetic variation influences how the brain-derived neurotrophic factor gene is expressed and regulated [4]. Although it does not directly alter the amino acid sequence of the protein, it is in high linkage disequilibrium with other functional variants like Val66Met [4]. This linkage means it serves as a strong proxy for variations that affect BDNF activity and secretion [4]. Consequently, it is associated with differences in body mass index, joint health, and response to psychiatric medications.
Key Insight: This variant is linked to both physical traits like grip strength and how the brain responds to psychiatric medications.
Location: BDNF. Chromosome 11 · 11p14.1 · 27.7 Mb
Estimated prevalence by population
Global 70.3%; European 63.2%; African 92.0%; East Asian 27.6%; South Asian 54.0%; Americas 68.2%; Ashkenazi 53.8%; Finnish 70.3%; Middle Eastern 62.8%; Amish 44.2%.
Estimated AA genotype frequency.
Global 26.0%; European 32.6%; African 7.8%; East Asian 49.9%; South Asian 39.0%; Americas 28.7%; Ashkenazi 39.1%; Finnish 27.1%; Middle Eastern 32.9%; Amish 44.6%.
Estimated AG genotype frequency.
Global 3.7%; European 4.2%; African 0.2%; East Asian 22.5%; South Asian 7.0%; Americas 3.0%; Ashkenazi 7.1%; Finnish 2.6%; Middle Eastern 4.3%; Amish 11.3%.
Estimated GG genotype frequency.
Showing effects for A/A genotype
Cardiovascular & Metabolic
Obesity & Body Composition
Body Mass Index. Evidence: 8/10. Source: PMID 25673413. Increased BMI.
Organ Systems
Bone, Joint & Connective Tissue Health
Osteoarthritis. Evidence: 6/10. Source: PMID 37247657. ~1.04x Risk.
Lifestyle, Fitness & Aging
Muscle Strength & Power
Grip Strength. Evidence: 6/10. Source: PMID 29691431. Lower Strength.
Pharmacogenomics
Antidepressant & Psychiatric Drug Response
Antipsychotic Response. Evidence: 5/10. Source: PMID 23433505. Typical Response.
Showing effects for A/G genotype
Body Mass Index. Evidence: 8/10. Source: PMID 25673413. Moderate BMI.
Osteoarthritis. Evidence: 6/10. Source: PMID 37247657. Typical Risk.
Grip Strength. Evidence: 6/10. Source: PMID 29691431. Typical Strength.
Antipsychotic Response. Evidence: 5/10. Source: PMID 23433505. Poorer Response.
Showing effects for G/G genotype
Body Mass Index. Evidence: 8/10. Source: PMID 25673413. Lower BMI.
Osteoarthritis. Evidence: 6/10. Source: PMID 37247657. Lower Risk.
Grip Strength. Evidence: 6/10. Source: PMID 29691431. Higher Strength.
What this genotype means for the people who carry it
Sample genotype: AA (Homozygous)
A common genetic profile carrying two copies of the A allele is associated with a higher average body mass index and an elevated risk of obesity [1]. Research indicates that this variation influences appetite regulation and satiety, making weight management more challenging [2]. Additionally, this genotype is linked to a slightly increased risk of developing osteoarthritis, particularly in the knees [3]. On the positive side, studies suggest that this profile is associated with a typical, more favorable response to antipsychotic treatments compared to other genotypes [4]. It is also associated with typical grip strength and a slightly higher likelihood of smoking behavior.
Higher average body mass index; Elevated risk of osteoarthritis; Typical response to antipsychotic medications.
Sample genotype: AG (Heterozygous)
An intermediate genetic profile carrying one A and one G allele is associated with a moderate risk of elevated body mass index and obesity [1]. This heterozygous state represents a middle ground for weight-related traits and joint health, showing a slightly lower risk of osteoarthritis than the AA genotype [2]. However, clinical studies have linked this profile to a poorer response or increased resistance to antipsychotic medications like clozapine [3]. This can make finding the right psychiatric treatment more complex if such medications are needed [3]. It is also associated with intermediate grip strength and a typical baseline for smoking behaviors.
Moderate risk of elevated body mass index; Slightly reduced response to antipsychotic medications; Typical physical grip strength.
Sample genotype: GG (Homozygous)
A less common genetic profile carrying two copies of the G allele is associated with a lower average body mass index and a reduced risk of obesity [1]. This genotype appears to support better weight management and a lower likelihood of developing osteoarthritis [2]. It is also linked to higher physical grip strength, suggesting a positive association with muscle function [3]. Despite these metabolic and physical benefits, clinical research has associated this profile with a significantly poorer response to antipsychotic medications [4]. This resistance to treatment means standard therapies may be less effective, which is important context for psychiatric care [4].
Lower average body mass index; Reduced risk of osteoarthritis; Poorer response to antipsychotic medications.
Variants with shared genetic architecture
rs6265 · BDNF Gene · Chr 11 · Brain Health and Plasticity
rs2030323 · BDNF Gene · Chr 11 · Weight and Appetite Control
rs2049045 · BDNF Gene · Chr 11 · Weight and Alcohol Risk
Evidence of association between brain-derived neurotrophic factor gene and bipolar disorder.
Genetic studies of body mass index yield new insights for obesity biology.
Influence of genetic variants associated with body mass index on eating behavior in childhood.
Lifetime risk and genetic predisposition to post-traumatic OA of the knee in the UK Biobank.
Biological Insights Into Muscular Strength: Genetic Findings in the UK Biobank.
Content updated August 2026.
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