Heterosis in COMT Val158Met Polymorphism Contributes to Sex-Differences in Children’s Math Anxiety

Abstract

Math anxiety (MA) is a phobic reaction to math activities, potentially impairing math achievement. Higher frequency of MA in females is explainable by the interaction between genetic and environmental factors. The molecular-genetic basis of MA has not been investigated. The COMT Val158Met polymorphism, which affects dopamine levels in the prefrontal cortex, has been associated with anxiety manifestations. The valine allele is associated with lower, and the methionine allele with higher, dopamine availability. In the present study, the effects of sex and COMT Val158Met genotypes on MA were investigated: 389 school children aged 7–12 years were assessed for intelligence, numerical estimation, arithmetic achievement and MA and genotyped for COMT Val158Met polymorphism. The Math Anxiety Questionnaire (MAQ) was used to assess the cognitive and affective components of MA. All genotype groups of boys and girls were comparable regarding genotype frequency, age, school grade, numerical estimation, and arithmetic abilities. We compared the results of all possible genetic models: codominance (Val/Val vs. Val/Met vs. Met/Met), heterosis (Val/Met vs. Val/Val plus Met/Met), valine dominance (Val/Val plus Val/Met vs. Met/Met), and methionine dominance (Met/Met plus Val/Met vs. Val/Val). Models were compared using AIC and AIC weights. No significant differences between girls and boys and no effects of the COMT Val158Met polymorphism on numerical estimation and arithmetic achievement were observed. Sex by genotype effects were significant for intelligence and MA. Intelligence scores were higher in Met/Met girls than in girls with at least one valine allele (valine dominance model). The best fitting model for MA was heterosis. In Anxiety Toward Mathematics, heterozygous individuals presented MA levels close to the grand average regardless of sex. Homozygous boys were significantly less and homozygous girls significantly more math anxious. Heterosis has been seldom explored, but in recent years has emerged as the best genetic model for some phenotypes associated with the COMT Val158Met polymorphism. This is the first study to investigate the genetic-molecular basis of MA.

How are different math knowledge presentations associated with math anxiety?

“…Math anxiety is one of the most important emotional problems in mathematics learning of students. Numerous studies have identified important individual and environmental factors that are closely related to math anxiety, including genetic sources, 6 emotion regulation, 7 cognitive development, 8 math anxiety from parents and teachers, 9 and so on. However, the primary factors responsible for the cause of math anxiety remain unclear.…”

MAOA‐LPR polymorphism and math anxiety: A marker of genetic susceptibility to social influences in girls?

“…The cognitive and affective dimensions of MA were assessed using the Math Anxiety Questionnaire (MAQ 70 ), which has been adapted and standardized for use in Brazil 14–16 . MAQ items are presented in one out of four types of questions: “How good are you at…”; “How much do you like…”; “How happy or unhappy are you if you have problems with…”, and “How worried are you if you have problems with…”.…”

“…36 Accordingly, valine at position 158 was associated with a more exploratory decision-making approach, which may reflect in impulsivity and schizophrenia, while methionine was associated with a more cautious or exploitative decision-making approach associated with higher working memory and anxiety. 35,37 Júlio-Costa and coworkers 15 However, an aspect to consider is the small amount of genetic variance in MA explained by the COMT Val158Met polymorphism in the Julio-Costa study, 4%, when compared to the 40% heritability estimated for MA. 11,12 Consequently, other candidate genes should be investigated, such as those involved in neurotransmitter synthesis, recycling, and degradation, and their receptors.…”

“…Yet, other evidence suggests sex‐specific genetic architectures in several traits, including some psychological characteristics, such as symptoms of internalizing disorders 32–34 . To the best of our knowledge, however, only one study investigated the genetic‐molecular basis of MA 15 . The results of this study suggest a sex dimorphic genetic foundation in the susceptibility to MA.…”

Integrating the Roles of Midbrain Dopamine Circuits in Behavior and Neuropsychiatric Disease

“…The catechol-O-methyltransferase (COMT) enzyme is responsible for DA dynamics, and polymorphisms of the COMT gene are also associated with treatment response, cortical activity, and cognitive functioning in schizophrenia [230,231]. Related to this, the relatively common COMT Val 158 Met polymorphism has been associated with differences in behavioral traits such as reward processing and anxiety [232,233]. Together, these genetic studies implicate DA metabolism machinery and thus region-specific DA levels in the expression of behavior in both clinically normal and neuropsychiatric contexts.…”