Schizophrenia risk is largely determined by genetic variation and is associated with altered development of several brain regions. Since there are likely thousands of genetic risk variants, the biology of risk and its effects on neural development cannot be determined by examining one gene at a time. Rather, it is important to understand how these genes converge into molecular pathways that determine overall risk. Genes converge into pathways because they are coordinated in response to environmental and physiologic factors. Hence, FLOURISH aims to identify biologically plausible pathways of convergence of genetic risk for schizophrenia along neural development in critical brain regions involved in schizophrenia risk. Gene Co-expression Network Analysis is effective to identify pathways of genes that are regulated, and thus expressed, together. FLOURISH will study how gene co-expression unfolds along the lifespan in the prefrontal cortex, hippocampus and striatum. Gene co-expression networks will then be associated with genetic variants to identify markers of pathway co-regulation. Genetic markers of pathways co-regulation will be combined into polygenic scores that will be tested as predictors of the structure and activity of the target brain regions assessed by magnetic resonance imaging. The action will consist of a training period (2 years) which Dr. Giulio Pergola will spend at the Lieber Institute for Brain Development (LIBD) at Johns Hopkins University, Baltimore, USA. LIBD is unique because of the unrivalled technology, expertise and research data regarding brain development. Dr. Pergola will be training about RNA analyses and return to the University of Bari Aldo Moro (UNIBA) in the final year, to validate his genetic discoveries by means of neuroimaging. UNIBA is currently setting up the largest neuroimaging center in southern Italy and plans to have Dr. Pergola build an imaging genomics team to promote personalized medicine in psychiatry.
Fields of science
Call for proposal
See other projects for this call