NEW BRUNSWICK, N.J. Rutgers geneticist Linda Brzustowicz and her colleagues have identified a specific DNA change that is likely to increase risk for developing schizophrenia in some people. It provides a potential mechanism that may be a point of entry for drug therapy, consistent with the growing trend of personalized medicine.
The research findings are reported in the April issue of the American Journal of Psychiatry (AJP). An accompanying editorial highlights the significance of this work.
Brzustowicz, a professor of genetics at Rutgers, The State University of New Jersey, and board-certified psychiatrist, said that the research has demonstrated a functional DNA change that increases gene expression. This conclusion is based on its presence in the genes of a Canadian study population of 24 families where multiple individuals had been diagnosed with schizophrenia. The gene in question, NOS1AP, previously known as CAPON, is one which Brzustowicz has been studying for six years.
The paper also presents an innovative statistical method, Posterior Probability of Linkage Disequilibrium (PPLD). This is the work of co-author Veronica Vieland of The Research Institute at Nationwide Children's Hospital, Columbus, Ohio. The new analytical technique quantifies the statistical evidence for association, in this case between the altered gene and schizophrenia. The researchers evaluated 60 variants of the gene or single nucleotide polymorphisms (SNPs).
"Our use of the PPLD was really helpful in sorting the evidence. It showed that of the 60 SNPs we were evaluating, three had a much higher probability of association with the illness," Brzustowicz said. "This paved the way for our next step doing a functional analysis using cells grown in culture which is much more labor intensive. We had reduced our 60 candidates down to a short list of three, which greatly simplified this next step."
Each of the three candidate SNPs
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