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New Research Suggests Genetic Component Contributes to Parkinsonís

In the largest genetic analysis of Parkinson’s disease (PD) undertaken to date, researchers have discovered five new genetic areas linked to Parkinson’s and confirmed that six other previously identified areas are in fact associated with the disease. The results appear in the February 2, 2011 online edition of The Lancet.

When studying genetics and Parkinson’s, scientists have typically focused on finding and studying singular gene mutations that directly cause the development of the disease. Thirteen of these mutations been found to date, but they affect only a small number of people living with Parkinson’s. In recent years, scientists have taken a new approach to genetics which involves studying the role of more common genetic variants that contribute to the development of, but do not cause Parkinson’s. Scientists suspect that these variants, when "added-up," e.g., when a person has several of them, may increase a person’s overall risk for Parkinson’s. Scientists study these variants by using genome wide association studies, or GWAS.  

With this in mind, a new genetic study was carried out by an international consortium of researchers led by Andrew Singleton, Ph.D., of the U.S. National Institutes of Health and Nick Wood, Ph.D., of University College, London. The scientists took advantage of five earlier GWAS studies that compared the DNA of people with Parkinson’s to that of healthy individuals, in search of differences that might contribute to the disease.  

The researchers pooled the data from these studies and used a statistical technique known as meta-analysis to analyze it anew. In total, the genetic information of more than 12,000 people with PD and some 21,000 heathy individuals was studied.  


Results

  • The scientists identified five new genetic loci, or areas associated with PD. These are places in DNA where a gene is located, but that may contain more than one gene. Variations can occur at different places in the gene.
  • The study confirmed six genetic loci previously associated with Parkinson’s.
  • The 20 percent of people who had the highest number of variations in the 11 loci associated with Parkinson's were 2.5 times more likely to develop Parkinson's than the 20 percent who had the lowest number of variations in these 11 areas.

What Does it Mean?

The authors of this study suggest Parkinson’s may have a stronger genetic component than previously realized. This signals a shift in thinking about the causes of the disease. Twenty years ago, PD was attributed entirely to environmental causes. Today, most scientists believe that a combination of environmental exposures and underlying genetic susceptibility leads to PD in most cases. 

Yet, it is important to note that the new findings will not translate soon into genetic tests for PD. The lifetime risk of developing PD for most people has been approximated to be 1.5 percent. Therefore, even for individuals identified in this study as having the highest risk, their chance of developing PD is only 3.5 percent - still quite low. This is in contrast with people who carry the genetic mutations in the gene LRRK2, who are at 30 percent risk for PD.

Further research is required in order to identify the biological pathway by which the 11 identified loci are associated with PD and to developing new therapies targeting these pathways.

 

Reference:International Parkinson Disease Genomics Consortium. Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genome-wide association studies. Lancet. 2011 Feb 1. [Epub ahead of print] PubMed PMID: 21292315. (http://www.ncbi.nlm.nih.gov/pubmed?term=21292315).

 

Source Date: Feb 14 2011