Public release date: 11-Nov-2012 [ | E-mail | Share ]

Contact: Karin Eskenazi ket2116@columbia.edu 212-342-0508 Columbia University Medical Center

New York, NY (November 11, 2012) Although schizophrenia is highly genetic in origin, the genes involved in the disorder have been difficult to identify. In the past few years, researchers have implicated several genes, but it is unclear how they act to produce the disorder. A new study by researchers at Columbia University Medical Center identifies affected gene networks and provides insight into the molecular causes of the disease.

The paper was published today in the online edition of the journal Nature Neuroscience.

Using an unbiased collection of hundreds of mutations associated with schizophrenia, the Columbia researchers applied a sophisticated computational approach to uncover hidden relationships among seemingly unrelated genes. The analysis revealed that many of the genes mutated in schizophrenia are organized into two main networks, which take part in a few key processes, including axon guidance, synapse function, neuron mobility, and chromosomal modification.

The study also uncovered an intriguing connection between schizophrenia and autism. "If we hadn't known that these were two different diseases, and had put all the mutations into a single analysis, it would have come up with very similar networks," said the study's senior author, Dennis Vitkup, PhD, associate professor in the Department of Biomedical Informatics, the Center for Computational Biology and Bioinformatics, and the Columbia Initiative in Systems Biology at Columbia University Medical Center. "It shows how closely the autism and schizophrenia genetic networks are intertwined," he added.

Although it will take time to translate the findings into practical treatments, the study provides insight into the molecular causes of schizophrenia. It also suggests that mutations associated with schizophrenia, autism, and probably many other psychiatric disorders, are likely to converge on a set of interrelated molecular processes.

Computer analysis uncovers genetic networks

To discover potential connections among genes mutated in schizophrenia, Dr. Vitkup and colleagues developed a computational approach, called NETBAG+, to identify networks of genes likely to be responsible for the same genetic phenotype. They then gathered the strongest mutations that had been observed in schizophrenia by other researchersincluding a set of de novo mutations recently described by a team of Columbia researchers led by Maria Karayiorgou, MD, and Joseph A. Gogos, MD, PhDand fed them into the program.

The program uncovered two genetic networks. Genes in the first network are involved primarily in axon guidance, synapse function, and cell migration. Genes in the second network are involved in chromosomal organization and remodeling.

Read more here:
Schizophrenia genetic networks identified; Connection to autism found

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