Unlike most other diseases, whose malfunctioning systems can often be clearly identified, psychiatric disorders affect brain regions whose precise locations are unknown. The largest known risk factor for bipolar disorder and schizophrenia is an inherited vulnerability. Thus, the specific goals of the Stanley Center genetics program are to identify genetic factors associated with this inherited liability as a mechanism to uncover novel biochemical pathways and new targets for drug discovery.

We will use state of the art methods for determining the extent to which common variation, rare variation, or structural variation (e.g. copy number changes) in humans contribute to bipolar disorder and schizophrenia. This includes identifying the specific biological consequences of disease-causing variation. A strong focus of the group is the development of novel methods for genetic analyses including gene-based and pathway based tests, imputation, segmental sharing (rare variants), epistasis, and predictive modeling. Close collaborations with Massachusetts General Hospital researchers facilitate exploration of genetic factors underlying treatment response or non-response.

We have completed genome-wide studies of bipolar disorder and schizophrenia of over 16,000 DNA samples. Strong preliminary results highlight the need for collection of much larger samples. In response to this, projects to dramatically enhance sample collections are being carried out with collaborators at the Karolinska Institute, University of North Carolina, and Cardiff University.

Project Leader: Pamela Sklar, MD, PhD