What you carry at this position in your DNA and what research says about it.
Stress and Focus: 6/10 evidence, 102 publications.
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Sample genotype (not yours): G/G
The Warrior: High Stress Resilience
Your body clears dopamine rapidly, which research links to staying focused under pressure. On average this genotype reports a somewhat higher pain threshold, while doing slightly less well on detailed memory tasks when calm. The differences are averages across groups and small next to everything else.
What this genotype means: High stress resilience; Higher pain tolerance; May respond less strongly to opioids.
Sample genotype (not yours): A/A
The Worrier: Enhanced Focus but Higher Stress Sensitivity
Slow dopamine clearance gives you an advantage in memory and attention tasks under calm conditions. However, this same trait makes you more sensitive to stress and physical pain.
What this genotype means: Enhanced working memory; Lower stress resilience; Higher pain sensitivity.
Sample genotype (not yours): G/A
The Balanced Profile: Moderate Stress Resilience and Focus
An intermediate rate of dopamine clearance provides a balanced mix of cognitive focus and stress resilience. This allows you to adapt well to both calm and high-pressure situations.
What this genotype means: Balanced dopamine clearance; Moderate stress resilience; Typical pain sensitivity.
Gene function and biological role
Gene Function: The COMT gene provides instructions for making catechol-O-methyltransferase, an enzyme that plays a critical role in breaking down neurotransmitters like dopamine, epinephrine, and norepinephrine [1]. This enzyme is particularly vital in the prefrontal cortex, the brain region responsible for planning, decision-making, and emotional control [1]. By regulating the levels of these chemical messengers, COMT helps maintain a delicate balance between cognitive performance and emotional stability [1]. Family and biochemical studies have long demonstrated that individual variations in COMT activity directly influence how people respond to social cooperation and cognitive challenges [2].
Variant Impact: The rs4680 variant, commonly known as Val158Met, is a missense mutation that substitutes the amino acid valine with methionine at position 158 of the COMT enzyme [1]. This single amino acid change alters the physical structure of the enzyme, reducing its activity to only about 25 percent of the typical level [1]. Because of this slower breakdown rate, individuals carrying the variant methionine allele experience a significant buildup of dopamine in the prefrontal cortex [1]. This functional difference has been shown to influence cognitive performance, pain sensitivity, and the risk of developing certain neuropsychiatric conditions [1] [3].
Read on the Stress & Focus page
Key Insight: The Worrier variant keeps dopamine levels high, boosting memory and focus under calm conditions but increasing vulnerability to stress.
Location: COMT. Chromosome 22 · 22q11.21 · 20.0 Mb
Estimated prevalence by population
Global 32.3%; European 23.2%; African 47.6%; East Asian 52.6%; South Asian 30.8%; Americas 35.5%; Ashkenazi 29.9%; Finnish 20.0%; Middle Eastern 28.2%; Amish 11.3%.
Estimated GG genotype frequency.
Global 47.3%; European 49.9%; African 42.8%; East Asian 39.8%; South Asian 49.4%; Americas 48.2%; Ashkenazi 49.6%; Finnish 49.4%; Middle Eastern 49.8%; Amish 44.6%.
Estimated GA genotype frequency.
Global 20.3%; European 26.8%; African 9.6%; East Asian 7.5%; South Asian 19.8%; Americas 16.4%; Ashkenazi 20.5%; Finnish 30.5%; Middle Eastern 22.0%; Amish 44.0%.
Estimated AA genotype frequency.
Showing effects for G/G genotype
Lifestyle, Fitness & Aging
Stress Response & Resilience
Stress Resilience. Evidence: 3/10. Source: PMID 8807664. High Resilience.
Neurology & Mental Health
Memory, Learning & Attention
Working Memory. Evidence: 3/10. Source: PMID 28273278. Typical Memory.
Addiction & Reward
Smoking Cessation. Evidence: 5/10. Source: PMID 18192898. Typical.
Organ Systems
Chronic Pain
Pain Sensitivity. Evidence: 3/10. Source: PMID 26489634. Lower Sensitivity.
Pharmacogenomics
Pain Medication Response
Opioid Pain Response. Evidence: 6/10. Source: PMID 19094200. Higher Tolerance.
Showing effects for A/A genotype
Stress Resilience. Evidence: 3/10. Source: PMID 8807664. Lower Resilience.
Working Memory. Evidence: 3/10. Source: PMID 28273278. Enhanced Memory.
Smoking Cessation. Evidence: 5/10. Source: PMID 18192898. Higher Success Rate.
Pain Sensitivity. Evidence: 3/10. Source: PMID 26489634. Higher Sensitivity.
Opioid Pain Response. Evidence: 6/10. Source: PMID 19094200. Higher Sensitivity.
Showing effects for G/A genotype
Stress Resilience. Evidence: 3/10. Source: PMID 8807664. Moderate Resilience.
Working Memory. Evidence: 3/10. Source: PMID 28273278. Slightly Enhanced.
Pain Sensitivity. Evidence: 3/10. Source: PMID 26489634. Typical Sensitivity.
Opioid Pain Response. Evidence: 6/10. Source: PMID 19094200. Typical Response.
What this genotype means for the people who carry it
Sample genotype: GG (Homozygous)
Possessing two copies of the G allele results in highly active COMT enzymes, which rapidly break down dopamine in the prefrontal cortex [1]. This rapid clearance prevents dopamine overload during stressful situations, which research associates with steadier performance in high-pressure conditions [1]. Research shows that individuals with this genotype, often called Warriors, show, on average, a somewhat higher pain threshold and less reactivity to negative or aversive stimuli [2]. However, because your baseline dopamine levels are lower under calm conditions, you may experience a slight disadvantage in tasks requiring sustained attention or working memory compared to Met carriers [2]. Studies also indicate that G/G individuals may respond less strongly to opioid medications like morphine for pain relief [3]. On the other hand, you may respond particularly well to certain wakefulness-promoting agents when sleep-deprived [1].
High stress resilience; Higher pain tolerance; May respond less strongly to opioids.
Sample genotype: AA (Homozygous)
Possessing two copies of the A allele results in a significantly less active COMT enzyme, which clears dopamine slowly from the prefrontal cortex [1]. This slow clearance leads to higher baseline dopamine levels, giving you a distinct advantage in complex cognitive tasks, working memory, and sustained attention under calm conditions [1] [2]. However, when stress strikes, the additional dopamine release can overload your system, leading to increased anxiety and a decline in performance [1] [3]. This Worrier profile is also associated with a lower physical pain threshold and higher emotional sensitivity to negative stimuli [1]. On the positive side, you may have a higher success rate with smoking cessation programs and greater sensitivity to opioid pain medications [4]. Managing stress through mindfulness, regular exercise, and avoiding excessive stimulants can help you maximize your cognitive strengths while keeping anxiety at bay [1].
Enhanced working memory; Lower stress resilience; Higher pain sensitivity.
Sample genotype: GA (Heterozygous)
Inheriting one copy of each allele results in intermediate COMT enzyme activity [1]. This balanced state means your brain clears dopamine at a moderate rate, avoiding the extremes of both the Warrior and Worrier profiles [1]. You likely experience a versatile mix of cognitive performance and emotional resilience, adapting well to changing environments [1]. Under normal conditions, your working memory and attention span are typical, while your ability to handle stress remains steady [2]. In medical settings, your response to pain and pain-relief medications like opioids is generally intermediate [3]. This balanced genetic background serves as a flexible foundation for both detailed cognitive tasks and moderate stress management [1] [2].
Balanced dopamine clearance; Moderate stress resilience; Typical pain sensitivity.
Variants with shared genetic architecture
rs165722 · COMT Gene · Chr 22 · Opioid Nausea Risk
rs4633 · COMT Gene · Chr 22 · Endometrial Cancer Risk
rs165599 · COMT Gene · Chr 22 · Mental Health Risk
The psychobiological regulation of social cooperation.
Epistasis between polymorphisms in COMT, ESR1, and GCH1 influences COMT enzyme activity and pain.
Association of COMT Val108/158Met genotype with smoking cessation.
Catechol-o-methyltransferase polymorphisms predict opioid consumption in postoperative pain.
Content updated September 2026.
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