Gene variant in people with African ancestry increases risk of Parkinson's disease

A novel mutation is present in 39 percent of Parkinson's disease patients of African heritage, but is virtually absent in those of European descent, a global genome wide association study has found.

The international collaboration comprised scientists from the University of Lagos in Nigeria, University College London, and the US National Institutes of Health (NIH) in Bethesda, Maryland. The researchers found that individuals with one or two copies of the GBA1 gene variant had a 1.5- or 3.5-times higher risk of developing Parkinson's disease, respectively, than those without.

Dr Sara Bandrés-Ciga, NIH researcher and joint first author of the paper published in The Lancet Neurology, said, 'We were completely surprised…The fact that the GBA1 variant had a significant association while others did not suggest that it is strongly tied to Parkinson's disease in this population.'

The worldwide consortium compiled genetic data from three different sources, totalling almost 198,000 individuals of either African or Afro-Caribbean ancestry. 1488 of these participants had Parkinson's disease and 196,430 were healthy controls. This data was compared with genetic data from 9230 Parkinson's disease cases and 4966 healthy controls of European ancestry.

The entire genomes of these individuals were sequenced, a process known as whole genome sequencing. The research team found that a specific variant in the GBA1 gene was present in 39 percent of Parkinson's disease patients of African descent but was very rare in those of European ancestry.

Dr Andrew Singleton, director of the Centre for Alzheimer's and Related Dementias at the NIH and joint corresponding author, said, 'These results support the idea that the genetic basis for a common disease can differ by ancestry, and understanding these differences may provide new insights into the biology of Parkinson's disease'.

GBA1 mutations have been identified in Parkinson's disease patients of other ancestries before, however, this variant is novel. The team also found that each copy of the allele caused the disease onset to occur three years earlier on average.

The GBA1 gene codes for an enzyme in the part of the cell that recycles proteins, called the lysosome. When the research team grew cells in the lab with the GBA1 mutation they found that this enzyme had a reduced activity, which can impair the overall function of the lysosome. This novel variant is thought to disrupt the enzyme activity in a distinct way to previously known GBA1 mutations.

Currently, there are clinical trials ongoing to investigate the effect of therapies that increase the activity of the GBA1 enzyme in Parkinson's disease patients.

'To effectively treat Parkinson's and truly any disease, we must study diverse populations to fully understand what the drivers and risk factors are for these disorders,' Dr Singleton added. 'Our hope is that results like these will provide researchers a roadmap for developing new genetic treatments and therapies for Parkinson's disease.'