Neil Risch
A team of geneticists, including UCSF's Neil Risch, reports in the January 26, 2006, issue of the
New England Journal of Medicine (NEJM) that a single mutation is a major cause of Parkinson's disease among Ashkenazi Jews - Jews of Eastern European origin who make up most of the world's Jewish population.
Until the last few years, there has been little evidence that vulnerability to Parkinson's disease (PD) is inherited, and the mutation the team studied has only recently been linked to Parkinson's.
The scientists found that the frequency of this mutation among Ashkenazi Parkinson's patients was 15 to 20 times higher than has been reported among patients of European ancestry generally. They found the mutation in more than 18 percent of the Ashkenazi Parkinson's patients screened in New York City, and in about 1.3 percent of the general Ashkenazi Jewish population.
Since the mutation itself is relatively rare, and since only about one person out of three with the mutation appears to get Parkinson's, the researchers estimate that the inherited defect accounts for about 20 percent of the disease in this population.
Ashkenazi Jews are genetically homogeneous enough to be identified by a number of genetic disease vulnerabilities, including Tay-Sachs and certain mutations for breast and ovarian cancer.
Earlier genetic studies identified a mutation common to both European and North African populations - a so-called "founder mutation" inherited from a common ancestor.
"From the evidence we have, it appears that this mutation has a Middle Eastern origin, as it is frequent not only in Jews, but Arabs, as well," said Risch, PhD, director of the Institute for Human Genetics at UCSF and co-author of the letter in NEJM. "It once again points out shared ancestry between these populations."
Risch is a leader in the fairly young field of genetic epidemiology, which seeks genetic patterns underlying disease vulnerability in diverse populations.
This mutation, in a gene known as LRRK2, was first identified in non-Jewish Europeans. A number of studies have found this mutation in only about 1 percent of European PD cases and less than one in 2,000 people from the general population. It is more common in PD cases with a family history, ranging up to 6 percent.
However, in Jews, the proportion of PD cases with a family history who carried the mutation was also much higher - 30 percent. "This might mean that genetics plays a greater role in Parkinson's in Jews because of this mutation, but that hasn't been resolved yet," Risch said.
"These results show that disease mutations, even for common diseases such as Parkinson's disease, can vary considerably from one population to another, and it is important to take this variability into account," Risch added. "Some groups will have this mutation, like Jews and Arabs, and some will not. That is likely to be the case with many other mutations - for Parkinson's or other common diseases."
Senior investigator on the report is Susan Bressman, MD, chair of neurology at Beth Israel Medical Center in New York and professor and vice chair of neurology at Albert Einstein College of Medicine. Lead author is Laurie Ozelius, PhD, associate professor of molecular genetics at Albert Einstein College of Medicine.
The research is supported by the Edwin and Caroline Levy Foundation, the Michael J. Fox Foundation for Parkinson's Research, the Thomas Hartman Foundation for Parkinson's Research and the National Institutes of Health.
Links:
LRRK2 G2019S as a Cause of Parkinson's Disease in Ashkenazi Jews
