From correlation to causality in psychiatric genetics

These are great times in psychiatric genetics! Through international collaboration and technological progress we are finally starting to identify the genes for psychiatric disorders. Using genome--‐wide association and next generation sequencing, we end up with genes and genetic variants, that are statistically correlated with disease. How can we go from this statistical definition of a link to a more biological understanding of the involvement of such genes and variants? And how can we make such findings useful for the patient? Different options that one would want to use, and what their contribution to solving the puzzle of psychiatric disease could be, will be discussed.

To really prove causality of a gene and variant downstream of GWAS or sequencing, animal models are required. Given the large numbers of genes one expects to find, a small, cheap and versatile model is required. Prof. Franke’s group has recently pioneered the use of Drosophila melanogaster, the fruit fly, as a model system for attention--‐deficit/hyperactivity disorder (ADHD). In her presentation, she will show, how genes involved in ADHD in humans also cause hyperactivity in the fly, and that this effect can be rescued by feeding methylphenidate, the most frequently prescribed ADHD medication, to the flies.

Having proven the involvement of a gene / variant, we are still far away from being able to use the genetic information in the clinic. Some rare variants might find their way into diagnostics, but the largest value of genetic findings for multifactorial disorders lies in the information they provide about the biological pathways underlying disease (etiology). This information can be used for the innovation and individualization of treatment. How this can be achieved through bioinformatics as well as through imaging genetics research --‐ linking genetics, brain function and behaviour --‐ will be discussed in a second part of the presentation.

Barbara Franke is a molecular biologist and professor of Molecular Psychiatry at the Radboud University in Nijmegen. She heads the Researchlab for Multifactorial Diseases at the Human Genetics Department of Radboud UMC and coordinates international consortia involved in ADHD genetics and imaging genetics research.

Lunch will be provided following the seminar – please RSVP to Ellie Pickering [e.pickering@exeter.ac.uk] so we can arrange suitable catering.