SP 5

Polygenic risk profiles for major psychiatric disorders in the general population

Many psychiatric disorders are heritable which has been shown in various family and twin studies. But it is only since sequencing of the human genome that there is a chance to identify the involved genes. Big studies with hundreds of patients scan millions of genetic variants, which may contribute to the disorders.
For some of them, e.g. schizophrenia or bipolar disorder, such risk genes could be identified. But there is not only one gene that causes a disorder, but rather a number of genes that belong to different systems of the human body. This makes it difficult to understand their individual pathogenic process.
In our sub-project we take the already identified risk genes as an initial step. We want to determine if these risk markers are also associated with other diseases and in this way understand the occurrence of the psychiatric disorders. This can be other psychiatric disorders like schizophrenia or bipolar disorder but also chronic diseases like type 2 diabetes, overweight or cardio-vascular disorders. The aim is to determine groups that are at higher risk for the specific disorder in an early stage.

Model of gene-environment interaction in psychiatric disorders
Genetic [A] as well as environmental factors [B] can idependently influece the risk for a specific disorder. But they also can only have an effect if they emerge jointly [C].

In addition to genetic factors, also environmental influences play a key role; especially with psychiatric disorders. These include early childhood trauma or stressful environment as well as lifestyle factors like smoking or obesity. We want to examine to what extend environment possess an additional risk or if specific genetic variants only have an effect in presence of the environmental factor (Figure 1). This is particularly important for the investigation of major depression, one of the most common psychiatric disorders. In contrast to other disorders no risk gene could be identified yet. Nevertheless, the knowledge about the biological mechanisms in psychiatric disorders and risk profiles can provide the chance for early interventions.


Keywords: Risk score, genetic risk, environmental risk, gene-environment interaction