Our society is increasingly dependent on tailoring education, work, and disease prevention to the talents and risks of the individual person. Brain structure and brain function are intricately related to both the talents and the cognitive limitations of the individual. Research has mapped various cognitive domains to structural and functional aspects of the brain, and has further shown that cognition, brain structure and brain function are strongly influenced by the genetic endowment of a person. In fact, we have recently witnessed a massive increase in reports on findings of associations between genes and various traits and cognitive processes. What is still critically lacking, however, is insight into the functional processes and consequences of genetic factors at the level of the brain. Such mechanistic insights are necessary to be able to translate genetic findings into new strategies for optimizing cognitive skills, preventing cognitive limitations, remedying cognitive deficits and in a broader scope, providing a structure for our society that preserves and promotes our invaluable human capital. This integration of whole genome studies and large-scale brain imaging creates a knowledge chain all the way from the genome to the brain to complex cognition. This is a new research field that we propose to call cognition genomics, or Cognomics.

The overall aim of this Cognomics investment proposal is to establish a resource of integrated behaviour - cognition - DNA - brain data of 7,000 adults from the general population and to make this resource publicly available to the national and international research community. This resource allows for the identification of common and rare genetic variants and epigenetic factors that influence cognitive processes at the level of brain structure and brain function.

We will recruit a stratified sample of 7,000 adults (age 18-40 years) from the general population around Nijmegen, Maastricht and Enschede, and characterize participants extensively in four cognitive domains: language, memory, cognitive control and social cognition. Brain imaging measures involve structural, diffusion weighted and resting state magnetic resonance imaging (MRI), MRI BOLD responses to language and memory tasks, as well as face and voice perception (total MRI session 1 hour). In addition, magnetoencephalographic recordings (MEG) will be done in a subgroup of 1,000 individuals. The other cognitive tasks will be administered offline. We will obtain DNA for genome-wide genotyping (both common and rare variants) and epigenetic profiling, and perform whole genome sequencing in 500 individuals. Genotype information will be imputed from the genotyping data in the remaining 6,500 individuals. Fibroblast cell lines for future transcriptomics and proteomics analyses, and for the establishment of induced pluripotent stem cells will be banked for 1,000 individuals. We also obtain background information about demographics, lifestyle, behaviour and personality, and environmental factors.