Parkinson’s disease gene variant found in study of some people of African ancestry

Aug. 24, 2023
NIH-supported, international study underscores importance of research of diverse populations.

A gene variant found almost exclusively in the genomes of people of African ancestry increases the risk of developing Parkinson’s disease, according to an international study of nearly 198,000 participants with this genetic background. Published in The Lancet Neurology, the study results suggest the risk may be linked to a variant in the gene encoding β-glucocerebrosidase (GBA1), a protein known to control how cells in the body recycle proteins.

The study was led by scientists at the National Institutes of Health; the University College, London; and the University of Lagos, Nigeria. Although more research is needed to understand the role of environmental and other factors in these populations, the scientists found that those who carry one copy of the gene are about 1.5 times more likely to have Parkinson’s disease than those who have no copies whereas those who carry two copies are about 3.5 times more likely.

For this project, the researchers conducted a genome wide association study (GWAS) involving 1,488 people who had Parkinson’s disease and 196,430 people who did not. NIH scientists worked with researchers from around the world who are part of the Global Parkinson’s Genetics Program (GP2), including the Black and African American Connections to Parkinson’s Study and the International Parkinson Disease Genomics Consortium (IPDGC) – Africa. GP2 is supported by the Aligning Science Across Parkinson’s (ASAP) initiative and implemented by The Michael J. Fox Foundation for Parkinson’s Research (MJFF).

Together the researchers collected DNA samples and analyzed genetic data from individuals primarily from Nigeria and four sites across the United States. These data were combined with de-identified genetic and phenotypic data from 195,587 people of African American or Afro-Caribbean descent who consented to participate in 23andMe research.

A preliminary analysis of the data showed a significant association between Parkinson’s disease risk and the newly identified variant of the GBA1 gene. A review of previous studies also showed that this new variant rarely appears in people of European and Asian descent, suggesting it is almost exclusively linked to African ancestry.

Further analysis of this study’s GWAS data suggested that the risk associated with the GBA1 variant is additive.

The results from this study suggest the new variant may alter lysosomal GBA1 activity in a previously unknown way. Most previously identified variants appear in the part of the genetic code that guides how the body manufactures glucocerebrosidase, an enzyme encoded by GBA1. This either disrupts the manufacturing process or alters the enzyme's activity. In contrast, this newly discovered Parkinson’s disease variant appears just outside of the coding region. Further research is needed to determine how the variant may change activity.

NIH release