Abstract
BackgroundGenetic 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.MethodsWe 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).ResultsResults 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.ConclusionsThese results demonstrate the key effect of genes by sex interaction, rather than their individual contribution, on the corpus callosum anatomy.
Highlights
Genetic polymorphisms play significant role in determining brain morphology, including white matter structure and may influence the development of brain functions
Our study demonstrated sexual dimorphism of fractional anisotropy (FA) values in various regions of the corpus callosum (CC) that was associated with COMT Val158Met polymorphism
We have not detected a main effect of genotype, we found that the COMT Val158Met polymorphism effect on FA in genu and rostral midbody of CC was moderated by sex, which adds an important dimension to the COMT functionality
Summary
Genetic polymorphisms play significant role in determining brain morphology, including white matter structure and may influence the development of brain functions. Developmental studies showed that dopamine (DA) is one of the earliest neuromodulators expressed in the developing brain that plays a role in the neuronal maturation and myelination (Bartzokis, 2011; Money & Stanwood, 2013). Genetic polymorphisms play a significant role in determining brain morphology, including white matter structure and may 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. 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
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