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Research Study Provides First Whole Genome Map of Genetic Variability in Parkinson's Disease

Rochester, MN—Mayo Clinic researchers in collaboration with scientists at Perlegen Sciences, Inc. and funded by The Michael J. Fox Foundation for Parkinson’s Research, have produced the first large-scale whole genome map of genetic variability associated with Parkinson’s disease.  Their results highlight changes in 12 genes that may increase the risk for Parkinson’s disease in some people.   Parkinson’s disease is a disabling and currently incurable disease that affects millions of people worldwide. 

Mayo Clinic and Perlegen Sciences will report their findings in the American Journal of Human Genetics.  The paper is now available online (

“This represents one of the first large-scale whole genome association studies of any disease,” said the study’s first author, Mayo Clinic neurologist Demetrius Maraganore, MD. “It is something we’ve wanted to do for years, and now we finally had the technology and funding to make it happen.  If confirmed, the findings may lead to new insights about the causes of Parkinson’s disease.”

Significance of the Findings

Both the findings and the technology that produced them are groundbreaking, representing one of the most comprehensive genetic studies of Parkinson’s disease to date, with nearly 200 million genetic tests (genotypes) completed.  To accomplish this, researchers initially studied the association of about 200,000 single-letter variations in the genome known as single nucleotide polymorphisms, or “SNPs” (pronounced “snips”) in patients with Parkinson’s disease. The study examined DNA from 775 persons with Parkinson’s disease (cases) and from 775 persons without Parkinson’s disease (controls).

“To be most effective, a whole genome association study requires accurate testing of a large number of SNP markers that are distributed across the human genome in a dense and informative pattern. In this respect, our collaborators at Perlegen have set a new standard,” said Dr. Maraganore.

“In one year, the Michael J. Fox Foundation and Mayo Clinic have generated results that will greatly focus future research efforts in Parkinson’s disease,” explained David Cox, MD, PhD chief scientific officer and co-founder of Perlegen Sciences. “If replication of only one of these findings leads to a better understanding of the causes of the disease, or improvements in the early detection or treatment of patients, we will have made significant progress.”

Noteworthy findings include:

  • Confirmation that variation in two previously known regions of the genome, PARK10 and PARK11, are likely associated with Parkinson’s disease susceptibility.
  • Identification of 10 additional SNPs that appear to be associated with Parkinson’s disease susceptibility.  Some of these are in or near genes with direct biological relevance to the disease.  For instance, one of these, the SEMA5A gene, may play an important role in both the development and programmed death of dopamine-producing nerve cells in the brain.  Selective degeneration of dopamine neurons in the brain is a hallmark feature of Parkinson’s disease.

Susceptibility genes are genes that may make some persons more or less likely to develop a disease, but do not outright cause the disease. The authors note that in this study, the size of the effect was small for any single SNP; combinations of gene variants or interactions with environmental factors may be necessary to develop Parkinson’s disease.

“This study represents the first large-scale attempt to assess the contribution of genes to susceptibility and development of Parkinson’s disease,” said Kenneth Olden, PhD, ScD, chief scientific advisor for The Michael J. Fox Foundation and former director of the National Institute of Environmental Health Sciences (NIEHS) of the National Institutes of Health (NIH).If confirmed, the finding of 12 potential susceptibility genes is significant. However equally significant is the fact that this comprehensive study found no strong single genetic determinant of Parkinson’s disease.”

The Michael J. Fox Foundation is presently organizing a large-scale validation study of the initial findings, through the existing Edmond J. Safra Global Genetics Consortia, the Foundation’s network of geneticists committed to sharing their population data on Parkinson’s disease.  The consortia will aggregate more than 10,000 patients and healthy unrelated control subjects, providing a powerful tool with which to validate these initial results.  This validation study is expected to be completed by the end of the year.

The Mayo Clinic/Perlegen Sciences study was funded by a one-year, $2.8 million grant under the Michael J. Fox Foundation’s LEAPS program, with funding provided by prominent Wisconsin businessman George Prescott and his family, and matched by the Foundation’s Board of Directors.  The work also benefited from long-standing funding from the National Institute of Environmental Health Sciences (NIEHS).  NIEHS supports the study of humans.

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