Dataset Information

Sex-specific effects of COMT Val158Met polymorphism on corpus callosum structure: A whole-brain diffusion-weighted imaging study.

ABSTRACT: BACKGROUND:Genetic polymorphisms play a significant role in determining brain morphology, including white matter structure and may thus influence the development of brain functions. The main objective of this study was to examine the effect of Val158Met (rs4680) polymorphism of Catechol-O-Methyltransferase (COMT) gene on white matter connectivity in healthy adults. METHODS:We used a whole-brain diffusion-weighted imaging method with Tract-Based Spatial Statistics (TBSS) analysis to examine white matter structural integrity in intrinsic brain networks on a sample of healthy subjects (N = 82). RESULTS:Results revealed a sex-specific effect of COMT on corpus callosum (CC): in males only, Val homozygotes had significantly higher fractional anisotropy (FA) compared to Met-carriers. Volume-of-interest analysis showed a genotype by sex interaction on FA in genu and rostral midbody of CC, whereby Val males demonstrated higher FA than Met females. CONCLUSIONS:These results demonstrate the key effect of genes by sex interaction, rather than their individual contribution, on the corpus callosum anatomy.

SUBMITTER: El-Hage W

PROVIDER: S-EPMC5607550 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Sex-specific effects of <i>COMT</i> Val158Met polymorphism on corpus callosum structure: A whole-brain diffusion-weighted imaging study.

El-Hage Wissam W Cléry Helen H Andersson Frederic F Filipiak Isabelle I Thiebaut de Schotten Michel M Gohier Benedicte B Surguladze Simon S

Brain and behavior 20170809 9

<h4>Background</h4>Genetic polymorphisms play a significant role in determining brain morphology, including white matter structure and may thus influence the development of brain functions. The main objective of this study was to examine the effect of Val158Met (rs4680) polymorphism of Catechol-<i>O</i>-Methyltransferase (<i>COMT</i>) gene on white matter connectivity in healthy adults.<h4>Methods</h4>We used a whole-brain diffusion-weighted imaging method with Tract-Based Spatial Statistics (TB ...[more]

PMID: 28948081

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Project description: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.

Project description:Recent years have seen a growing interest in relating MRI measurements to the structural-biophysical properties of white matter fibers. The fiber g-ratio, defined as the ratio between the inner and outer radii of the axon myelin sheath, is an important structural property of white matter, affecting signal conduction. Recently proposed modeling methods that use a combination of quantitative-MRI signals, enable a measurement of the fiber g-ratio in vivo. Here we use an MRI-based g-ratio estimation to observe the variance of the g-ratio within the corpus callosum, and evaluate sex and age related differences. To estimate the g-ratio we used a model (Stikov et al., 2011; Duval et al., 2017) based on two different WM microstructure parameters: the relative amounts of myelin (myelin volume fraction, MVF) and fibers (fiber volume fraction, FVF) in a voxel. We derived the FVF from the fractional anisotropy (FA), and estimated the MVF by using the lipid and macromolecular tissue volume (MTV), calculated from the proton density (Mezer et al., 2013). In comparison to other methods of estimating the MVF, MTV represents a stable parameter with a straightforward route of acquisition. To establish our model, we first compared histological MVF measurements (West et al., 2016) with the MRI derived MTV. We then implemented our model on a large database of 92 subjects (44 males), aged 7 to 81, in order to evaluate age and sex related changes within the corpus callosum. Our results show that the MTV provides a good estimation of MVF for calculating g-ratio, and produced values from the corpus callosum that correspond to those found in animals ex vivo and are close to the theoretical optimum, as well as to published in vivo data. Our results demonstrate that the MTV derived g-ratio provides a simple and reliable in vivo g-ratio-weighted (GR*) measurement in humans. In agreement with theoretical predictions, and unlike other tissue parameters measured with MRI, the g-ratio estimations were found to be relatively stable with age, and we found no support for a significant sexual dimorphism with age.

Dataset Information

Sex-specific effects of COMT Val158Met polymorphism on corpus callosum structure: A whole-brain diffusion-weighted imaging study.

Publications

Sex-specific effects of <i>COMT</i> Val158Met polymorphism on corpus callosum structure: A whole-brain diffusion-weighted imaging study.

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