New approach speeds up discovery of Parkinson's-related genes

Over 60 genes linked to Parkinson's disease have been identified using a new multidisciplinary approach.

Parkinson's disease is a neurodegenerative disorder that causes problems with movement and is believed to be caused by a combination of genetic and environmental factors. While genome-wide association studies (GWAS) have already identified some genes that contribute to Parkinson's disease risk, they only account for around a third of the known heritability of the condition.

'Our success in identifying so many new variants and the remarkable congruence in the results we obtained at each step of this screen supports this is as a powerful method to identify and validate new Parkinson's disease candidate genes,' said Professor Juan Botas who led the research at Texas Children's Hospital and Baylor College of Medicine.

To try to understand the full genetic components of the causation and progression of Parkinson's disease, Professor Botas and his team developed a novel high-throughput, multidisciplinary approach to identifying genes that affect disease risk.

Starting with 160 possible genes from GWAS and transcriptome-wide association studies (TWAS), these were reduced to 80 using computer analysis. Then they looked at the expression patterns of these 80 genes in the blood and brain tissues of Parkinson's disease patients. Finally, they used a model organism (drosophila fruit flies) to establish a functional relationship between genes and whether they were involved in biological processes affected by the disease.

Their results, published in the journal Human Molecular Genetics, show that they identified 50 Parkinson's disease risk genes and 14 neuroprotective genes.

This approach significantly sped up the normally arduous process of identification and functional verification of the role of specific genes in a genetic disorder. The authors think that it could be used to look at other diseases that are affected by large numbers of genes:

'As long as genomic information is readily available, this approach can be applied broadly to a wide range of complex genetic disorders and so, we anticipate this study to have a wide impact on disease areas much beyond Parkinson's disease,' said Professor Botas.