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
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.
been working with a set of DNA samples from patients with schizophrenia and
healthy volunteers from the Ashkenazi population, which has inbred for many
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
“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
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
Schizophrenia and bipolar disorder are severe
psychiatric disorders that affect 1 percent to 4% of the global
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