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Parkinsons Disease can Be Predicted by Metabolic Pathway

A new Mayo Clinic study provides strong evidence that the joint effects of common DNA variations in several genes that encode proteins in a pathway explain why some persons get Parkinsons disease while others dont. It even predict with great accuracy at what age people might develop their first symptoms.

This represents a major paradigm shift from single gene studies to genomic pathway studies of complex diseases, says Demetrius Maraganore, M.D., the Mayo Clinic neurologist and Parkinsons disease specialist who led the study.

The authors say traditional genetic studies have either discovered rare single gene mutations that cause Parkinsons disease only in isolated families, or have identified common single gene variants that are only weakly associated with the disease and inconsistently across populations.

By examining a large cluster of related genes, we found patterns that make people up to 90 times more likely to develop Parkinsons than the average person, says study co-author Timothy Lesnick, a Mayo Clinic biostatistician. The size of the effects that we observed for genes within a pathway and the statistical significance of the predictive models were unprecedented.

The models were highly effective in predicting age of onset of the disease: by age 60, 91 percent of patients in the highest-risk group already had Parkinsons, while only 11 percent of patients in the lowest-risk group did. By age 70, every member of the highest-risk group had the disease, whereas two-thirds of patients in the lowest-risk group still were disease-free. Members of the highest-risk group typically developed Parkinsons more than 20 years earlier than the lowest-risk group.

The researchers speculate that common genetic variations within the same biological pathway might also contribute to a persons risk of developing other brain diseases; disorders such as Alzheimers disease, Tourettes syndrome, dyslexia, epilepsy and schizophren
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