Grant: Operating Grant

In Canada, approximately 250,000 people suffer from schizophrenia. In an attempt to unlock the primary causes of this disease, over the last 30 years, research efforts focused on DNA sequence variation. However, a detailed re-analysis of the scientific literature on major psychiatric disease indicates that another group of factors may be of major importance in the origin of schizophrenia. These factors do not change the structure of DNA, but affect the way genes function, often reducing or enhancing the product a gene normally produces. This study of changes affecting gene expression is an emerging field of research known as "epigenetics", or "epigenomics" when investigation expands beyond the specific area of a gene and across many regions of the whole genome. Using cutting-edge microarray technology that allows millions of measurements to be taken in a single experiment, the DNA modification status of the entire non-repetitive genome in 400 DNA samples will be investigated. The samples are from people with schizophrenia and a comparison group of people without the disease. These experiments will complement traditional genetic research and, hopefully, the work will reveal why certain gene variants appear to increase schizophrenia risk in some people but not others. If this comprehensive epigenomic study substantially changes our understanding of the molecular mechanisms underlying schizophrenia, it could lead to new diagnostic methods and treatments for major psychiatric illness.