Ashkenazi genes key to new study

A new study on the genetics behind schizophrenia and bipolar disorder has found that a tiny genetic difference can increase the risk of being afflicted with the diseases, a difference only found thanks to the unique genetics of Ashkenazi Jews.

“I’ve always known we have a unique demographic history,” said study team leader Dr. Todd Lencz, an associate investigator at the Feinstein Institute for Medical Research, part of the North Shore-Long Island Jewish Health System.

Modern Ashkenazi Jews often have a keen interest in genetic research due in part to the comparative prevalence of some genetic diseases within the community, a result of the relatively uniform background of the community.

“Ashkenazi Jews are used to the idea of genetically testing for a disease,” Lencz said. “More used to the idea than most people on the planet.”

For this study, the idea was to exploit the similarities of Ashkenazi genetics to tease out what the still existing differences meant for their health.

“The goal was to identify genetic risk factors for schizophrenia and bipolar disorder,” Lencz said.

At first the study had focused just on schizophrenia, but was later expanded to include bipolar disorder due to the overlap in the genetics of the two disorders making a combined study of both worthwhile. The team looked at the gene called NDST3 and found that with just one chemical changed in the complex ladder of DNA composing it, the chances of having schizophrenia or bipolar disorder were slightly increased.

“There are millions of variations in genes and typically the differences are very subtle,” Lencz said. “It takes thousands of tests to detect differences but it’s easier when they are closely related.”

“It’s really interesting that the research is looking at Ashkenazi Jews like me,” said Matt, a young lawyer living in Northern Virginia, who said he was diagnosed with bipolar disorder when he was a teenager.

Matt, who asked that his last name not be included, uses medication and therapy to control his bipolar disorder and said it rarely causes him much trouble but he remembers how the mood swings would affect him and how even knowing what was causing it didn’t help.

“It would just be the utter inability to imagine anything good happening, and then I’d start to get really angry and yell a lot,” he said of his pre-treatment days. “That doesn’t happen really anymore but yeah I still worry about it.”

Of the approximately 2,500 Ashkenazi Jews whose DNA was used in the study, a little more than 900 presented the NDST3 risk factor, but when compared with more than 25,000 people from all kinds of backgrounds, only about a quarter displayed the irregular gene.

“Ashkenazi homogeneity enhances our ability to detect these risk factors,” Lencz said.

While the differences between the farthest related humans is tiny, evolutionarily speaking, when checking for individual differences between peoples’ genetics, closer relations help highlight hidden changes from mutation.

“All Ashkenazim today, are all just derived from a few hundred ancestors,” Lencz said, explaining that the number is probably between 200 and 300 individuals from between 700 and 800 years ago.

“We’re all close cousins,” he said.

Despite the prevalence of the gene, Lencz said it is only one of many risk factors, and a minor one at that, raising the chances of expressing the diseases by perhaps a tenth of one percent.

“The increase is very subtle,” Lencz said. “It wouldn’t be something to test for.”
What’s important about their findings is how it helps researchers understand the development of the disease, and may lead to new ideas about treatment.

“It’s incredibly advantageous in trying to identify the genes behind the diseases,” Lencz said.

“Mine is under control luckily, but it would be great if there were even better treatments,” Matt said.

The utility of using Ashkenazi genes applies beyond his own work, Lencz said. The Ashkenazi Genomics Consortium pools its resources to be able to get the most out of studying the genome.

“It will give us new approaches to treating the diseases.”