What you carry at this position in your DNA and what research says about it.
Pain and Stress Sensitivity: 5/10 evidence, 37 publications.
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Sample genotype (not yours): A/A
Higher Pain Sensitivity and Enhanced Focus
This genotype is associated with higher sensitivity to physical pain and an increased risk of chronic pain conditions. However, it may also support better focus and working memory due to higher baseline dopamine levels.
What this genotype means: Increased sensitivity to physical pain; Higher risk of developing chronic pain conditions; Potentially greater sensitivity to opioid pain medications.
Sample genotype (not yours): A/G
Typical Pain Sensitivity and Balanced Cognition
This genotype represents a balanced intermediate state, showing typical pain sensitivity and average baseline dopamine levels. It does not significantly elevate the risk for chronic pain conditions.
What this genotype means: Typical baseline pain threshold; Standard response to common pain medications; Balanced baseline dopamine levels.
Sample genotype (not yours): G/G
Lower Pain Sensitivity and Typical Focus
This genotype is associated with lower sensitivity to physical pain and a reduced risk of chronic pain conditions. It leads to rapid dopamine clearance, which may result in typical cognitive processing.
What this genotype means: Higher physical pain tolerance; Lower risk of developing fibromyalgia; Standard baseline cognitive focus.
Gene function and biological role
Gene Function: The COMT gene provides instructions for making the catechol-O-methyltransferase enzyme, which plays a crucial role in the brain and nervous system [1]. This enzyme is responsible for breaking down catecholamines, a class of neurotransmitters that includes dopamine, epinephrine, and norepinephrine [2]. By regulating the levels of these chemical messengers, the gene helps control cognitive functions, stress responses, and how the body processes pain signals [3]. Variations in this gene can significantly alter enzyme activity, leading to differences in baseline neurotransmitter levels and individual physiological responses [4].
Variant Impact: The rs6269 variant is a single nucleotide polymorphism located in the 5-prime regulatory region of the COMT gene [5]. This specific genetic change influences the rate at which the COMT enzyme is produced, thereby altering overall enzymatic activity [6]. The G allele is strongly linked to high enzyme activity, which leads to rapid clearance of dopamine and norepinephrine [7]. Conversely, the A allele is associated with lower enzyme activity, resulting in higher baseline levels of these neurotransmitters and altered pain processing [3].
Key Insight: The same genetic variant that makes you more sensitive to physical pain also tends to increase your baseline dopamine levels, which can enhance focus and working memory under normal conditions.
Location: COMT. Chromosome 22 · 22q11.21 · 20.0 Mb
Estimated prevalence by population
Global 39.0%; European 35.9%; African 39.0%; East Asian 45.7%; South Asian 44.9%; Americas 44.8%; Ashkenazi 27.6%; Finnish 47.8%; Middle Eastern 33.0%; Amish 47.6%.
Estimated AA genotype frequency.
Global 46.7%; European 48.0%; African 46.9%; East Asian 43.8%; South Asian 44.2%; Americas 44.3%; Ashkenazi 49.9%; Finnish 42.7%; Middle Eastern 48.9%; Amish 42.8%.
Estimated AG genotype frequency.
Global 14.3%; European 16.1%; African 14.1%; East Asian 10.5%; South Asian 10.9%; Americas 10.9%; Ashkenazi 22.6%; Finnish 9.5%; Middle Eastern 18.1%; Amish 9.6%.
Estimated GG genotype frequency.
Showing effects for A/A genotype
Organ Systems
Chronic Pain
Pain Sensitivity. Evidence: 4/10. Source: PMID 19193196. Higher Sensitivity.
Fibromyalgia. Evidence: 4/10. Source: PMID 26849490. Increased Risk.
Pharmacogenomics
Pain Medication Response
Morphine Response. Evidence: 5/10. Source: PMID 19094200. Higher Sensitivity.
Neurology & Mental Health
Cognitive Performance
Cognitive Function. Evidence: 4/10. Source: PMID 23178897. Enhanced Focus.
Showing effects for A/G genotype
Pain Sensitivity. Evidence: 4/10. Source: PMID 19193196. Moderate Sensitivity.
Fibromyalgia. Evidence: 4/10. Source: PMID 26849490. Typical Risk.
Morphine Response. Evidence: 5/10. Source: PMID 19094200. Typical Response.
Cognitive Function. Evidence: 4/10. Source: PMID 23178897. Typical Cognition.
Showing effects for G/G genotype
Pain Sensitivity. Evidence: 4/10. Source: PMID 19193196. Lower Sensitivity.
Cognitive Function. Evidence: 4/10. Source: PMID 23178897. Lower Focus.
What this genotype means for the people who carry it
Sample genotype: AA (Homozygous)
Having two copies of the A allele results in significantly lower COMT enzyme activity [1]. This slower clearance leads to higher baseline levels of dopamine and norepinephrine in the brain [2]. While higher dopamine can enhance executive function and working memory, the accompanying elevation in norepinephrine is linked to heightened pain sensitivity [3]. Research indicates that individuals with this genotype are more susceptible to chronic pain conditions like fibromyalgia [4]. Additionally, clinical studies suggest that patients with this genotype may be more sensitive to morphine for pain relief [5].
Increased sensitivity to physical pain; Higher risk of developing chronic pain conditions; Potentially greater sensitivity to opioid pain medications.
Sample genotype: AG (Heterozygous)
Carrying one A allele and one G allele results in moderate COMT enzyme activity [1]. This intermediate level of activity maintains a balanced clearance rate of dopamine and norepinephrine in the prefrontal cortex [2]. Consequently, individuals with this genotype typically experience average pain sensitivity and standard cognitive processing [3]. They do not exhibit the heightened pain vulnerability associated with the A/A genotype, nor do they have the rapid dopamine clearance of the G/G genotype [4]. Response to pain medications like morphine is generally typical and within standard therapeutic ranges [5].
Typical baseline pain threshold; Standard response to common pain medications; Balanced baseline dopamine levels.
Sample genotype: GG (Homozygous)
Having two copies of the G allele results in high COMT enzyme activity [1]. This rapid clearance of catecholamines keeps baseline levels of dopamine and norepinephrine lower in the brain [2]. Lower norepinephrine levels are associated with a higher pain threshold and a reduced risk of developing chronic pain syndromes [3]. Studies show that individuals with this genotype are less likely to report severe pain or develop fibromyalgia [4]. However, the rapid clearance of dopamine means they may not experience the cognitive focus advantages seen in A allele carriers under normal conditions [5].
Higher physical pain tolerance; Lower risk of developing fibromyalgia; Standard baseline cognitive focus.
Variants with shared genetic architecture
rs165722 · COMT Gene · Chr 22 · Opioid Nausea Risk
rs4633 · COMT Gene · Chr 22 · Endometrial Cancer Risk
rs4680 · COMT Gene · Chr 22 · Stress and Focus
Genetic contributions to pain: a review of findings in humans.
Pain sensitivity in fibromyalgia is associated with catechol-O-methyltransferase (COMT) gene.
Effects of catechol-O-methyltransferase on normal variation in the cognitive function of children.
Content updated August 2026.
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