Tuesday, July 22, 2014
An international team of researchers has identified more than 100 locations in the human genome associated with the risk of an individual developing schizophrenia, according to a study published online in the journal Nature this week.
The findings advance the knowledge of schizophrenia on the molecular level, and provide critical information about the biological pathways underlying the illness — which has been poorly understood until now.
By understanding the molecular and cellular pathways involved in schizophrenia, researchers may be able to develop enhanced therapies that target multiple symptoms. Currently available medications only treat psychosis, which is just one of an array of symptoms of schizophrenia. This area of drug development has had few advances in the past 60 years.
The study, which represents the largest genomic study of psychiatric illness to date, was conducted by the Schizophrenia Working Group of the Psychiatric Genomics Consortium, a multinational collaborative effort founded in 2007. The group conducts broad-scale analyses of genetic data for psychiatric disease.
Central analysis for the study was performed primarily at the Broad Institute at MIT and Harvard University. However, a total of 55 datasets from more than 40 different contributors were needed to conduct the analysis, one of which was provided by a team from Virginia Commonwealth University School of Medicine, led by Brien Riley, Ph.D., associate professor of psychiatry, and human and molecular genetics.
In the genome-wide association study, the team examined more than 80,000 genetic samples from schizophrenia patients and healthy volunteers. They found 108 specific locations in the human genome associated with risk for schizophrenia. Eighty-three of those loci had not previously been linked to the disorder.
Further, in a statement released by the Broad Institute, “the study implicates genes expressed in brain tissue, particularly those related to neuronal and synaptic function. These include genes that are active in pathways controlling synaptic plasticity – a function essential to learning and memory – and pathways governing postsynaptic activity, such as voltage-gated calcium channels, which are involved in signaling between cells in the brain.”
“The publication of this paper is a watershed event in the study of schizophrenia,” said Riley, director of the Molecular Genetics Lab at the Virginia Institute for Psychiatric and Behavioral Genetics at VCU. “The results of the study are incredibly important because of the number of novel genes implicated in schizophrenia risk and the potential for innovation in both biological understanding and therapeutic development.”
“However, the fundamentally different model of performing genomic research with this degree of worldwide collaboration is of equal importance because it shows how genetic disorders once thought to be impossibly complex can be studied successfully,” Riley said.
According to Riley, the VCU group, in collaboration with researchers at Trinity College Dublin in Ireland, Queens University Belfast and the Wellcome Trust in the United Kingdom, contributed nearly 4,000 of the 80,000 individual case and control samples studied.
Work conducted at the VCU Virginia Institute for Psychiatric and Behavioral Genetics was supported by a grant from the U.S. National Institute of Mental Health, grant number MH083094, and by the Wellcome Trust.
Core funding for the Psychiatric Genomics Consortium comes from the U.S. National Institute of Mental Health, along with numerous grants from the governmental and charitable organizations, as well as philanthropic donations.
To read the study abstract visit: http://www.nature.com/nature/journal/vaop/ncurrent/full/nature13595.html.
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