NEWYORK, NY — A large-scale validation study of Parkinson’s disease risk funded by The Michael J. Fox Foundation has found no association between PD risk and 13 SNPs (single-nucleotide polymorphisms — single-letter changes to the DNA code) implicated in PD susceptibility by a prior study. The results were published online today by the journal Lancet Neurology and are supported by those of several smaller studies that have generally been unable to confirm the original findings.
“With these results in hand, we can feel quite confident that no single common variation in our DNA explains a large percentage of Parkinson’s risk in the general population,” said Gene Johnson, PhD, chief scientific advisor to The Michael J. Fox Foundation. “The results do not imply, however, that genetics plays no role whatsoever in sporadic PD.”
That is because these 13 SNPs, as well as others, could still be found to interact with other genetic and/or environmental factors and play some role in PD risk. To allow researchers to mine the data for further insight into the underlying genetics of PD, the dataset from the prior study and the follow-up study will be made available online.
“The Foundation was able to use pre-existing consortia already in place to organize and complete the validation study within a year of the original study,” said Deborah W. Brooks, the Foundation’s president and CEO. “There would have been a great deal of excitement among both patients and researchers if the 13 SNPs had been validated as new avenues of inquiry. But this major attempt to validate genetic risk seen in the first genome-wide study of Parkinson’s disease has still done a great deal of good in terms of informing and unifying future steps.”
In 2003, MJFF funded a large-scale study through its LEAPS initiative to survey the entire human genome for SNPs potentially associated with greater risk for PD. That study, led by Demetrius Maraganore, MD, of the Mayo Clinic and David Cox, MD, PhD, of Perlegen Sciences, was published in September 2005. The researchers examined 443 pairs of siblings where one sibling had PD, as well as 332 pairs of unrelated PD-affected and healthy individuals. The results implicated 13 SNPs as possibly associated with altered risk for idiopathic PD, though the overall contribution of any one SNP was low, suggesting that no single common genetic variation could explain a large percentage of PD risk in the sample population studied.
The Foundation organized and launched the validation study in fall 2005 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 aggregated more than 12,000 DNA samples from PD patients and healthy unrelated control subjects, providing a powerful tool with which to validate the initial results.
Additionally, a separate study also published online by Lancet Neurology today that looked at almost twice as many SNPs as the original study from Dr. Maraganore found no single SNP to contribute greatly to PD risk. These data are also being made available online for research use.
“Genetics continues to be a major focus for the PD field,” concluded Brian Fiske, PhD, the Foundation’s associate director of research programs. “Much of what we know about possible underlying mechanisms of PD cause and pathogenesis has come through studies of genes linked to the disease through studies of families with a clear history of the disease. However, the role of genetics in the larger, general, population of sporadic PD remains unclear. The results of these recent large-scale studies imply that the answer will be complex, and the subject of vigorous study and debate.”