PHG Foundation logo

Genetic risk underlying Parkinson's Disease

Archived news

Parkinson's disease (PD) is a chronic degenerative disorder of the central nervous system that often impairs the sufferer's motor skills, speech, and other functions. Parkinson’s is caused by degeneration of the basal ganglia, an area of the brain, and by low production of the neurotransmitter, dopamine. Most PD patients are over 50, and one in 500 people in the UK suffer from the condition according to the Parkinson’s Disease Society. The common form of  PD (as opposed to much rarer Mendelian forms of Parkinsonism) is a complex disorder caused by multiple genetic and environmental factors. Previously, genome-wide association studies (GWAS) for PD have shown some evidence for association of several genetic variants with disease risk, but not at statistically significant levels.
Recently, two independent GWA studies, one led by researchers in Japan [Satake et al.(2009)Nat Genet 15 November doi:10.1038/ng.485] and another by collaborators from USA and Europe [Simón-Sánchez et al. (2009) Nat Genet 15 November doi:10.1038/ng.487] have detected strong links between PD and several genetic variants, and have compared their results.
Satake et al. and colleagues studied more than 2,000 Japanese PD cases and 18,000 control subjects. They identified new susceptibility loci on chromosomes 1 and 4, designated the PARK16 and BST1 loci. The genes SNCA and LRRK2 (on chromosomes 4 and 12 respectively) also showed significant association with risk of Parkinson’s. Simón-Sánchez et al. and colleagues studied more than 5,000 PD cases and 8,000 controls of European ancestry and observed strong associations at the SNCA and MAPT gene loci.
When the data from the two studies were compared, it was found that variants of PARK16, SNCA and LRRK2 genes were associated with increased risk of Parkinson’s in both Japanese and ancestral European populations, while variants of the BST1 gene and MAPT locus were associated with PD risk only in Japanese and ancestral European populations, respectively. Therefore the authors concluded that the findings reflect “population differences in the genetic heterogeneity of PD aetiology”.
There is supporting evidence for how the susceptibility genes identified by the two groups may contribute to the aetiology of Parkinson’s disease. For example, the SNCA gene encodes a protein involved in RNA processing or stability, which is also the main component of Lewy body, a pathological hallmark of typical PD. SNPs in the BST1 gene have been linked with dysfunction of neurones (nerve cells), and the PARK16 region contains functionally interesting candidate genes for PD aetiology. Presently, although medical treatments may improve symptoms of Parkinson’s Disease, there are none that can slow down or halt the disease’s progression. It is hoped that a better understanding of genetic mechanisms underlying this disease including discovery of new susceptibility loci, will lead to strategies that may help to delay or potentially prevent the disease.

Genomics and policy newsletter

Sign up