Beyond Classical Inheritance: The Influence of Maternal Genotype upon Child's Brain Morphology and Behavior

Abstract

Genetic variance has been associated with variations in brain morphology, cognition, behavior, and disease risk. One well studied example of how common genetic variance is associated with brain morphology is the serotonin transporter gene polymorphism within the promoter region (5-HTTLPR). Because serotonin is a key neurotrophic factor during brain development, genetically determined variations in serotonin activity during maturation, in particular during early prenatal development, may underlie the observed association. However, the intrauterine microenvironment is not only determined by the child's, but also the mother's genotype. Therefore, we hypothesized that maternal 5-HTTLPR genotype influences the child's brain development beyond direct inheritance. To test this hypothesis, we investigated 76 children who were all heterozygous for the 5-HTTLPR (sl) and who had mothers who were either homozygous for the long (ll) or the short allele (ss). Using MRI, we assessed brain morphology as a function of maternal genotype. Gray matter density of the somatosensory cortex was found to be greater in children of ss mothers compared with children of ll mothers. Behavioral assessment showed that fine motor task performance was altered in children of ll mothers and the degree of this behavioral effect correlated with somatosensory cortex density across individuals. Our findings provide initial evidence that maternal genotype can affect the child's phenotype beyond effects of classical inheritance. Our observation appears to be explained by intrauterine environmental differences or by differences in maternal behavior.

Maternal VDR variants rather than 25-hydroxyvitamin D concentration during early pregnancy are associated with type 1 diabetes in the offspring

“…However, the maternal genotype has previously been shown to be associated with, for example, the child's brain morphology [32], cognitive development [33], risk of autism [34] and atopic dermatitis [35]. The fact that type 1 diabetes-associated autoantibodies that precede the diagnosis of type 1 diabetes can appear only months after birth [36] suggests a fetal programming of the disease.…”

Genetic and environmental modulation of neurodevelopmental disorders: Translational insights from labs to beds

“…Although all children carried the L/S genotype, somatosensory cortex grey matter density and fine motor task performance were greater in children of the SS mothers [190]. In another human study, familial analyses of the tryptophan hydroxylase 1 gene TpH1 mutation carriers (that have deficiency in serotonin production in the periphery, but not in the brain) revealed that offspring of mothers carrying TpH1 mutations exhibited higher ADHD scores and related symptoms than did controls or offspring of fathers with the corresponding TpH1 mutations [79].…”

“…Another important factor in fetal neural development is maternal genotype. For example, maternal SERT promoter region 5-HTTLPR genotype affects the development of children, with their neuroimaging phenotypes and cognitive performance differing between the 5-HTTLPR SS and LL mothers [190].…”

Perceived Parenting Mediates Serotonin Transporter Gene (5-HTTLPR) and Neural System Function during Facial Recognition: A Pilot Study

“…It is known that parental genotypes are related to negative parenting behaviours and of course children share the genotypes of their parents [ 29 ]. A recent study found that links between 5-HTTLPR gene of mother and child were related to child brain morphology and behavioural performance [ 46 ].…”