Parkinson's Disease Risk Indicators Found in Diverse Tissues

Tiny changes in DNA that have been linked to Parkinson's disease, the second most common neurodegenerative disorder after Alzheimer's, were found not only in brain cells, where they were expected, but also in liver, fat, immune and developmental cells.

Parkinson’s disease (PD) is the second most common neurodegenerative disorder, affecting about 1% of those over the age of 60 and classically, PD was considered a movement disorder with akinesia, rigidity, tremor and postural instability as the predominant motor features.

Scientists at the Van Andel Research Institute (Grand Rapids, MI, USA) and their collaborators investigated single-nucleotide polymorphisms SNPS) which were integrated with comprehensive data from the Roadmap Epigenomics Mapping Consortium (REMC) for 77 tissues and cell types and 1000 genomes using FunciSNP software.

The team found 12 loci across several tissue types that were particularly enriched or full of SNPS indicating an increase in risk. Only one locus was identified in the substantia nigra, the part of the brain where dopamine-producing neurons die. Other loci were found in liver, fat, immune and developmental cells. It is the first time this type of genome-wide analysis has been used to investigate Parkinson's disease.

Although much more work must be done to unravel exactly how these loci affect risk, there are interesting parallels between the team's findings and recent work done by others investigating Parkinson's. For example, three of the risk loci were found in immune cells, a promising finding as evidence suggests that Parkinson's may be linked to inflammation, the immune system's reaction to help fight off potential threats.

Patrik Brundin, MD, PhD, director of Center for Neurodegenerative Science and one of the study's authors, said, “Only a small percentage of Parkinson's cases are familial and have a clear and well-defined genetic inheritance. The remaining cases develop the disease seemingly at random. The emerging view is that Parkinson's is more of a syndrome, as a defined set of clinical symptoms and some shared features of brain pathology, with a diverse set of underlying causes. One surprising finding in our study is that only one gene locus was clearly linked to the brain while others were associated with tissues throughout the body. This supports the emerging theory that Parkinson's is a disorder that can be caused by disruptions in cellular processes in many locations, not just one. Furthermore, for the disease to develop in one person there has to be an unfortunate combination of a genetic predisposition and, as yet undefined, environmental insults.” The study was published on July 27, 2016, in the journal Scientific Reports.

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Van Andel Research Institute