NARSAD Young Investigator Grantee, Alexander Niculescu, III, M.D., Ph.D. has led a team of scientists at the Indiana University School of Medicine in pinpointing the genes most responsible for schizophrenia. To identify and prioritize the genes reported Tuesday in the Nature journal Molecular Psychiatry, the researchers combined data from several different types of studies. These included genome-wide association studies, gene expression data derived from human tissue samples, genetic linkage studies, genetic evidence from animal models, and other work. This approach, called convergent functional genomics, has been pioneered by Niculescu and colleagues, and relies on multiple independent lines of evidence to implicate genes in clinical disorders.

Evaluating the biological pathways in which the genes are active, the researchers also proposed a model of schizophrenia as a disease emerging from a mix of genetic variations affecting brain development and neuronal connections along with environmental factors, particularly stress and developed a prototype predictive test for schizophrenia. The prototype test was able to predict whether a person was at a higher or lower risk of schizophrenia in about two-thirds of cases.

"For first time we have a comprehensive list of the genes that have the best evidence for involvement in schizophrenia," said Niculescu. "By better understanding the genetic and biological basis of the illness, we can develop better tests for it as well as better treatments. The future of medicine is not just treatment but prevention, so we hope this work will move things in the right direction."

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