GBA1 found as Parkinson’s risk factor in African, African admixed populations

Key takeaways:

• Researchers analyzed genetics of more than 197,000 persons of African or African admixed ancestry.
• A genetic risk factor was found in GBA1 in the study population, but not in those of European descent.

The B-glucocerebrosidase protein was a novel risk factor for Parkinson’s disease in African or African admixed populations and may assist in targeted treatments for these populations, according to a study published in The Lancet Neurology.

“To effectively treat Parkinson’s, we must study diverse populations to fully understand what the drivers and risk factors are for these disorders,” Andrew B. Singleton, PhD, study co-author and director of the NIH Intramural Center for Alzheimer’s Related Dementias, said in a related press release. “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.”

Singleton, along with lead author Mie Rizig, PhD, of the department of neuromuscular diseases at University College London Queen Square Institute of Neurology, sought to perform a genome-wide assessment in African and African admixed individuals to clarify the genetic architecture of PD in these underserved populations.

Their study included 197,918 individuals of African and African admixed ancestry with PD (n=1,488) and healthy controls (n=196,430) selected from cohorts from the Global Parkinson’s Genetics Program, the International Parkinson’s Disease Genomics Consortium Africa and 23andMe. Researchers analyzed and characterized factors such as ancestry-specific risk, differential haplotype structure and admixture, coding and structural genetic variation and enzymatic activity, focusing on the B-glucocerebrosidase (GBA1) protein.

Researchers identified a common risk factor for PD (overall meta-analysis OR for risk of Parkinson’s disease 1.58 [95% CI, 1.37–1.80], P = 2.397×1014) and age at onset at the GBA1 locus, rs3115534-G (age at onset =–2.00 [SE=0.57], P = 0.0005, for African ancestry and =–4.15 [0.58], P = 0.015, for African admixed ancestry), which was rare in non-African or non-African admixed populations.

“By addressing the genetic complexity underlying these under-represented populations, our study represents a valuable resource for identifying and tracking GBAI carriers that might prove to be relevant for enrollment in target-specific Parkinson’s disease clinical trials,” Rizig and colleagues wrote.

Reference:

• Parkinson’s disease gene variant found in study of some people of African ancestry. https://irp.nih.gov/news-and-events/in-the-news/parkinsons-disease-gene-variant-found-in-study-of-some-people-of-african. Published Aug. 23, 2023. Accessed Sept. 1, 2023.