Understanding how genetic variants influence the risk of developing schizophrenia is one of the major challenges in biomedical research. An important step forward comes from a study published in Nature Genetics, which identified 766 genes associated with the disorder, including 641 that had never previously been implicated in schizophrenia in genome-wide studies.
The research is the result of a large international collaboration involving Professor Silvia Pellegrini of the Department of Clinical and Experimental Medicine at the University of Pisa. Among the principal co-authors is Dr Giulia Grassi of the IMT School for Advanced Studies Lucca, who is carrying out her research project under Professor Pellegrini’s supervision.
The study used genetic data from more than 100,000 individuals collected by the Psychiatric Genomics Consortium, the world’s largest international research network dedicated to investigating the genetic basis of psychiatric disorders.
“The results suggest that genetic risk for schizophrenia does not depend on the action of individual genes, but rather on their complex interactions,” explains Professor Giulio Pergola of the University of Bari Aldo Moro, who led the project. “The newly identified genes regulate important mechanisms underlying brain function, including communication between neurons, molecular transport and the activation of immune processes.”
“Two innovative models for analysing gene-expression data were developed, capable of capturing long-range interactions between genes that are activated together in the brain,” comments Silvia Pellegrini. “The integration of this information enabled us to identify hundreds of new genes associated with the disorder and to gain a more precise understanding of the biological mechanisms underlying it. This approach could also be applied to other complex diseases, helping us better understand how the information contained in DNA influences gene function and disease risk, with the goal of identifying new therapeutic opportunities.”
The study was the result of a broad international collaboration involving universities and research centres across Europe, the United States, Canada, Australia and Brazil. In addition to the University of Pisa and the IMT School for Advanced Studies Lucca, the collaboration included the University of Bari Aldo Moro and the University of Turin — partners with the University of Pisa in the PRIN 2020 project, one of the study’s funding sources — as well as the Lieber Institute for Brain Development, Johns Hopkins University, the University of Trento, Kore University of Enna and IRCCS Oasi of Troina.
