An international study led by the University of Exeter Medical School has made advances in understanding the ways in which genetic risk factors alter gene function in schizophrenia. The study, published online on August 30, 2016 in Genome Biology and funded by the Medical Research Council (MRC), combined genetic sequence information with measures of gene regulation in schizophrenia patients and matched controls. The article is titled “An Integrated Genetic-Epigenetic Analysis of Schizophrenia: Evidence for Co-Localization of Genetic Associations and Differential DNA Methylation.” Schizophrenia is an inherited, neuropsychiatric disorder characterized by episodes of psychosis and altered brain function. Despite previous research successfully identifying genetic variants associated with schizophrenia, scientists remain uncertain about which genes cause the condition and how their function is regulated. The new study, which used blood samples from 1,714 individuals, is the largest of its kind. It has helped to clarify which specific genes are actually affected by the genetic variants associated with schizophrenia, and provides a blueprint for researchers to undertake similar analyses for other complex diseases. The r esearch team included collaborators from King's College London, University College London and the University of Aberdeen, as well as colleagues in Finland, China, Germany, and the Netherlands. The team focused on both the underlying genetic sequence and DNA methylation, an epigenetic mark that regulates both gene expression and function. By profiling genetic and regulatory variation in the same samples, the group found that many of the genetic variants previously found to be associated with schizophrenia have potential effects on gene regulation.
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