Approved research

Understanding polygenic liability through connectome-based genetic imaging.

Lay summary

We are interested in the genetic foundation of behavior and psychiatric disorders. Most psychological traits, including those affected in psychiatric disorders, are heritable. While heritability points towards genetic mechanisms, it does not imply genetic determinism that escapes educational and therapeutic interventions. In order for such interventions to be effective, it is imperative to understand the pathways between genes and behavior. This will help us to identify promising targets for a wide range of possible interventions. The past years have seen an ever-growing number of genome-wide studies that are increasingly successful in providing comprehensive lists of regions of our DNA that are statistically linked to behavior and disorders. While these studies point at promising candidates, it is at present still unclear how the identified genetic variations affect behavior or result in psychiatric illness. One promising level of investigation is the human brain. Genes are expressed in brain cells and shape communication paths and activation patterns throughout the brain. Behavior, behavioral disposition, and disorders of thought and behavior emerge from neural communication and activation patterns. Understanding how neural circuits are affected by genetic risk variants can therefore help to bridge the current gap between genes and behavior. We plan to use the Biobank resource to map neural circuits throughout the human brain in the form of connectome maps. Connectome maps are wiring diagrams that provide information on communication paths and communication patterns at the brain level. We then plan to investigate which parts of the connectome are altered in individuals with high genetic liability for certain psychological traits and disorders. With such knowledge, we will be able to investigate the relationship between aspects of connectome functioning with traits and disorders, and inform the design and evaluation of educational programs, psychological interventions such as cognitive-behavioral therapy and even aid drug discovery for pharmacological treatment regimes.