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

• Published in: Brain and behavior Vol. 7; no. 9; pp. e00786 - n/a
• Main Authors: El‐Hage, Wissam, Cléry, Helen, Andersson, Frederic, Filipiak, Isabelle, Thiebaut de Schotten, Michel, Gohier, Benedicte, Surguladze, Simon
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.09.2017; Wiley Open Access; John Wiley and Sons Inc
• Subjects: Adult; Anisotropy; Attention deficit hyperactivity disorder; Brain - anatomy & histology; Catechol O-Methyltransferase - genetics; COMT polymorphism; Corpus Callosum - anatomy & histology; Diffusion Magnetic Resonance Imaging; Diffusion‐weighted imaging (DWI); Dopamine; Estrogens; Female; Genetics; Genotype; Genotype & phenotype; Human genetics; Humans; Life Sciences; Male; Males; Memory; Middle Aged; Neurobiology; Neurons and Cognition; Organ Size - physiology; Original Research; Polymorphism; Polymorphism, Single Nucleotide; sex effect; Sex Factors; Studies; tract‐based spatial statistics (TBSS); white matter; Young Adult; white matter; sex effect; Diffusion‐weighted imaging (DWI); COMT polymorphism; tract‐based spatial statistics (TBSS)
• ISSN: 2162-3279; 2162-3279
• DOI: 10.1002/brb3.786

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. This study demonstrated sexual dimorphism of fractional anisotropy (FA) values in various regions of the corpus callosum (CC) that was associated with COMT Val158Met polymorphism. Male Val homozygotes had significantly higher white matter integrity compared with Met‐carriers, whereas there was no genetic effect on FA values in females.