Researchers find new risk factor for two psychiatric disorders in Ashkenazi genes

Israeli, American researchers publish work on new genetic risk factor for schizophrenia, bipolar disorder.

By JUDY SIEGEL-ITZKOVICH
Hebrew U 370 (photo credit: Courtesy of the Hebrew University)
Hebrew U 370
(photo credit: Courtesy of the Hebrew University)
Israeli and American researchers investigating a healthy Ashkenazi Jewish population have identified a new genetic risk factor for schizophrenia and bipolar disorder (manic-depression).
Their work, just published in Nature Communications, was reported by scientists at the Feinstein Institute for Medical Research in Manhasset, New York and at the Hebrew University of Jerusalem.
The researchers identified the defect in the gene, named NDST3, by studying more than 25,000 individuals.
Conducting the study was a team led by Dr. Todd Lencz at the Zucker Hillside Hospital’s department of psychiatry research and the Feinstein Institute, and HU’s Dr. Ariel Darvasi, who has studied Ashkenazi populations for disorders for many years.
Lencz has been working with a set of DNA samples from patients with schizophrenia and healthy volunteers from the Ashkenazi population, which has inbred for many centuries.
Ashkenazim represent a unique population for study because of their relatively short (less than 1,000-year) history and limited population. This history results in a more uniform genetic background in which to identify diseaserelated variants.
“This study again demonstrates the value of our Ashkenazi cohort,” said Lencz. “It is notable that the genetic variant was replicated in samples of various ethnicities from all around the world, but the effects were strongest in the Ashkenazi cohort, presumably due to their unique genetic history.”
Lencz’s team reported that the genetic variant, which changes a single “letter” of the DNA code, alters the expression of the gene NDST3. This gene is critical to neurodevelopmental processes such as axon formation and synaptic function.
These findings shed new light on the genetic architecture and potential therapeutic targets for the treatment of psychiatric disease.
Schizophrenia and bipolar disorder are severe psychiatric disorders that affect 1 percent to 4% of the global population.
Studies have shown that the two disorders are likely to have a large overlap in genetic risk factors, but only a small portion of this genetic risk has been identified.
A grant from the US National Institute of Mental Health supported this work.
More recently, Lencz’s and Darvasi’s work on Ashkenazim received an additional $3 million from the NIMH, as well as grants from the Brain and Behavior Foundation and the Binational Science Foundation.