One of the essential organizational principles of invertebrate and vertebrate neurobiology is asymmetric organization of functional or structural properties within the central nervous system. For handedness, the most widely investigated form of hemispheric asymmetries in humans, single gene explanations have been the most popular ontogenetic model in the past. However, while classic family studies suggest heritability of up to 0.66 for handedness, molecular genetic studies revealed only few specific genes contributing to a small amount of phenotypic variance. The divergence between heritability estimates from family studies and results obtained from molecular studies has been referred to as the missing heritability problem, which could partly be accounted for by heritable epigenetic mechanisms. Here, we review recent findings describing non-genetic influences on handedness from conception to childhood. We aim to advance the idea that epigenetic regulation might be the mediating mechanism between environment and phenotype. Recent findings on molecular epigenetic mechanisms indicate that particular asymmetries in DNA methylation might affect asymmetric gene expression in the central nervous system that in turn mediates handedness. We propose that an integration of genes and environment is essential to fully comprehend the ontogenesis of handedness and other hemispheric asymmetries.

Schmitz J, Metz GAM, Güntürkün O, Ocklenburg S. Beyond the genome—Towards an epigenetic understanding of handedness ontogenesis. Progress in Neurobiology. 2017 159: 69-89.