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University of Essex helps unravel the complex #biology of schizophrenia

01 Sep University of Essex helps unravel the complex #biology of schizophrenia

An international study which involved the University of Essex has made advances in understanding the ways in which genetic risk factors alter gene function in schizophrenia.

The study, published in Genome Biology and funded by the Medical Research Council, combined genetic sequence information with measures of gene regulation in schizophrenia patients and matched controls.

Schizophrenia is an inherited, neuropsychiatric disorder characterised 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 study, led by the University of Exeter Medical School, used blood samples from 1,714 individuals and 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 team included collaborators from Essex, 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 which 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. The team also identified epigenetic changes in 27 of 105 regions of the genome previously implicated in schizophrenia, prioritising specific genes for further functional studies and as potential targets for novel treatments.

Professor Leo Schalkwyk, Head of the Genomics Research Group at Essex, said: “Schizophrenia is a devastating illness with a clear genetic component that has been very difficult to study. Genetic studies have been successful but have indicated that there are hundreds of genes that each have a small effect on the risk of schizophrenia.

“This study of epigenetic differences between some of the same case and control individuals is helping to unravel the complicated biology of this illness.”

Professor Jonathan Mill, of the University of Exeter Medical School, who led the research, said: “This study highlights the power of integrating different types of genomic data to better understand how disease-associated DNA sequence variation actually influences the way in which genes function. Although our study focussed on schizophrenia, we’re now applying this approach to other types of complex disease.”