The left and right sides of the human brain are specialized for different kinds of information processing, and much of our cognition is relatively lateralized to one side or the other. One of the most strikingly lateralized functions is language, many aspects of which are predominantly processed in the left hemisphere. Despite asymmetry being a fundamental organizing feature of the human brain, the genetic mechanisms underlying it remain almost completely unknown. In addition, language impairment, schizophrenia and autism are sometimes linked to abnormal brain asymmetry, and the degree of asymmetry for some cognitive tasks is linked to performance on these tasks. It is therefore likely that identifying genes involved in brain asymmetry will yield new insights into molecular processes in cognitive variability and psychiatric disease.

Functional asymmetries are correlated with structural asymmetries in the brain. We work with the Brain Imaging Genetics (BIG) dataset which is a growing database of human subjects with brain MRI and whole genome genotypes (currently roughly 1500 subjects have MRI and genetic data). The project is supported jointly by teams at the Donders Institute for Brain, Cognition & Behavior, the Department of Human Genetics of the Radboud University Medical Center, and the Max Planck Institute for Psycholinguistics. We use volumetrics, voxel-based morphometry, and diffusion tensor imaging to measure various asymmetries in the brain, and then carry out genome-wide analyses to test for rare and common genetic variants that affect these asymmetries. Our work so far has focussed on identifying genes implicated in asymmetrical development of subcortical structures which, in turn, might cascade into more widespread brain asymmetries later in development (as is the case in fish).

We are also interested in epigenetics in relation to brain asymmetries. Epigenetics refers to chemical modifications of DNA and its associated proteins in the cell, and is a level of complexity over and above the variation that exists in DNA sequences. Individual differences in epigenetic states at some genes may underlie cognitive variability in the population. Dr Francks previously identified a gene called LRRTM1 linked to handedness and susceptibility to schizophrenia. This gene is expressed in a parent-of-origin-specific manner, which suggests a role for epigenetic control. We are currently screening for epigenetic abnormalities at this gene in psychiatric disease and aim to relate this to language cognition.