Why some people cope better with stress and some fold under the pressure? This can be explained with COMT gene and rs4680 marker. It is one of the most important markers associated with intelligence and personality. COMT gene codes for the COMT enzyme which breaks down dopamine in the prefrontal cortex. This is the part of the brain that is responsible for planning, decision making, cognitive ability, problem-solving, reasoning. Rs4680 marker has two alleles G and A (risk allele). Please remember that this one marker does not define You as a person thou, but is related to the statistical findings.
A : A
A : G
G : G
COMT activity is about 30% lower in females than in males. This also means that dopamine levels are about 30% higher in females. So during stress dopamine levels in females get higher resulting in worsened performance. On the other hand, during stress, dopamine levels in males get to optimal levels improving their performance. Therefore, having A allele (risk allele) can be helpful for men, but not for women.
Stressful life events can be risk factors for poor performance among A allele carriers, because during stress A allele carriers tend to pay too much attention to gains. On the other hand parental warmth is a protective factor for good performance among G:G genotype.
A:A genotype means that you are a “worrier”. A allele carriers have 3-4 fold decrease in COMT enzyme activity which results in higher dopamine levels in the prefrontal cortex. Under stress dopamine levels rise. If you have increased dopamine production, it results in very high dopamine levels in your body during stress. This can cause worsened performance under stress.
A allele carriers are more susceptible to stress, have lower pain threshold and are more prone to anxiety. Risk allele carriers are more likely to develop depression after stress or having experienced childhood maltreatment. About 37% of the population carries at least one copy of the A allele.
Characteristics of “worrier”:
Lower emotional resilience
Better at attention tasks, focussing (but not under stress)
Gets more pleasure out of life
Worse handling stress or pain
Better reading comprehension
Increased verbal fluency for males
Better cognitive function when not under stress (better attention and processing of information)
Decreased verbal fluency for females
Better response to placebos
Less cooperative, empathic and helpful
Fine motor skills
Higher risk for ADHD (Attention-deficit hyperactivity disorder)
Better ability to aim
Risk for cocaine dependance
Lower risk for alcoholism
Higher sensitivity to mercury
A:G genotype means that you have intermediate dopamine levels. You still have higher dopamine levels in prefrontal cortex, but not as high as “worrier”. People with intermediate dopamine levels make more balanced decisions under stress when compared with “worriers”.
People with A:G genotype tend to be more balanced compared to “worrier” and “warrior”.
G:G genotype means that you are a “warrior”. This genotype causes increase in COMT enzyme activity which results in lower dopamine levels in the prefrontal cortex. Lower dopamine producers perform better under stress because they have optimal level of dopamine in their body during stress. “Warriors” have higher risk for developing schizophrenia, especially when using cannabis.
Characteristics of “warrior”:
Better handling of stress or pain
Less pleasure out of life
More cooperative, empathic and helpful
Worse executive function/processing information, but not under stress
Better at learning languages
Worse fine motor skills
Higher emotional resilience
Decreased verbal fluency for males
Increased verbal fluency for females
Better working memory
Increased risk for breast and endometrial cancer
Get more easily into hypnosis
Risk for schizophrenia
More childhood depressive symptoms
DRUG RESPONSES G alleles had a worse response to paxil/paroxetin.
Parkinson’s patients may respond to lower doses of levodopa and benefit from vitamin B6.
- Mandelli, L. et al. Interaction between serotonin transporter gene, catechol-O-methyltransferase gene and stressful life events in mood disorders. Int J Neuropsychopharmacol 10(4), 437–47 (2007).
- Aberg, E. et al. The functional Val158Met polymorphism in catechol-O-methyltransferase (COMT) is associated with depression and motivation in men from a Swedish population–based study. J Affect Disord 129(1–3), 158–66 (2011).
The information provided in this article is based on published SNP (single nucleotide polymorphism) data and is for educational purposes only. Most published studies about genetic variants in the DNA explain only a small part of the heritability of a trait or disease risk, and often do not take into account how different variants may interact with each other. In addition, many published studies do not account for medical history or environmental, dietary, microbial, or lifestyle factors, which may alter true risk for any trait or disease.
The relevance of each article may vary based on ethnicity. Nothing in the genetic article should be used for medical self-diagnosis or self-treatment. The information provided should not be considered complete, nor should it be relied on to suggest diagnosis or treatment of a particular individual. You should always get the advice of your doctor or other appropriate health care professional if you have any questions about diagnosis, treatment, prevention, mitigation, or cure of any medical condition, phenotype, condition, impairment, or the status of your health.
An allele is a variant form of a gene that is located at a specific position, or genetic locus, on a specific chromosome. Humans have two alleles at each genetic locus, with one allele inherited from each parent.
A chromosome is a thread-like structure of DNA that carries hereditary information, or genes. Human cells have 22 chromosome pairs plus two sex chromosomes, giving a total of 46 per cell.
The proportion of individuals in a population having a disease or characteristic. Prevalence is a statistical concept referring to the number of cases of a disease that are present in a particular population at a given time, whereas incidence refers to the number of new cases that develop in a given period of time.
DNA, or deoxyribonucleic acid, is the main component of chromosomes and the carrier of genetic information in nearly all living organisms. DNA is made up of molecules called nucleotides. Each nucleotide contains a phosphate group, a sugar group and a nitrogen base. The four types of nitrogen bases are adenine (A), thymine (T), guanine (G) and cytosine (C).
A hereditary unit consisting of a sequence of DNA that occupies a specific location on a chromosome. Genes are transferred from a parent to offspring, and are responsible for the physical and heritable characteristics or phenotype of an individual.
An alteration in the most common DNA nucleotide sequence. The variant can be benign, pathogenic or of unknown significance. SNPs are the most common type of genetic variation.
The genetic makeup of an individual organism. It may also refer to just a particular gene or set of genes carried by an individual. The genotype determines the phenotype, or observable traits of the organism.
The odds ratio is a way of comparing whether the odds of a certain outcome is the same for two different groups. In this report, the odds ratio estimates the probability of a condition occurring in a group of people with a certain genetic variant compared to a group of people without that variant.
An odds ratio of 1 means that the two groups are equally likely to develop the condition. An odds ratio higher than 1 means that the people with the genetic variant are more likely to develop the condition, while an odds ratio of less than 1 means that the the people with the variant are less likely to develop the condition.
A description of an individual’s physical characteristics, including appearance, development and behaviour. The phenotype is determined by the individual’s genotype as well as environmental factors.
POPULATION ALLELE FREQUENCY
The allele frequency represents the incidence of a gene variant in a population. Alleles are variant forms of a gene that are located at the same position, or genetic locus, on a chromosome.
Single nucleotide polymorphisms, frequently called SNPs, are the most common type of genetic variation among people. A SNP is a variation in a single nucleotide that occurs at a specific position in the genome.
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