Gene Variant That Increases Parkinson’s Disease Risk Found in People of African Ancestry

A variant – found almost exclusively in people of African ancestry – of the gene that encodes β-glucocerebrosidase increases the risk of developing Parkinson’s disease, reports a new study published in The Lancet Neurology.

Parkinson’s disease is a growing issue

According to the World Health Organization, the prevalence of Parkinson’s disease has doubled since 1998, with over 8.5 million individuals now living with the disease. Symptoms of Parkinson’s disease include tremor, cognitive impairment, sleep disorders and dementia, which worsen over time.

Mutations in more than 20 genes have been linked to rare, inherited cases of Parkinson’s disease, and pathogenic variants in more than 100 genes have been associated with the onset and progression of more common forms of the disease.

The majority of studies investigating the impact of genomic alterations on Parkinson’s disease have been carried out on Eurocentric study populations. Senior author of the new study, Dr. Andrew Singleton, said: “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.”

Increasing diversity

In the new study, researchers conducted genome-wide association studies in nearly 198,000 individuals of African ancestry, 1488 of whom had Parkinson’s disease. The data stemmed from study participants primarily from Nigeria and the United States whose data is part of the Global Parkinson's Genetic Program, and from people of African American or Afro-Caribbean descent from a 23andMe study.

They identified a significant association between a newly identified variant of the β- glucocerebrosidase (GBA1) gene and increased Parkinson’s risk. Previous studies have shown that this variant rarely appears in people of European or Asian ancestry.

“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,” said Singleton.

The authors also highlighted that the increased risk presented by the GBA1 variant is additive, with individuals who carry one copy of the gene being 1.5 times more likely and people with two copies being about 3.5 times more likely to develop Parkinson’s when compared to people with no copies.

Variants of GBA1 that have previously been associated with Parkinson’s disease have mutations to the coding region of the gene, which disrupt either how glucocerebrosidase is manufactured or its activity.

Although further research is needed to elucidate how the new GBA1 variant alters the gene’s activity, the researchers propose that this may be different from how previously identified variants impact the glucocerebrosidase gene, as the mutation falls outside of the coding region.

“Our results represent a good first step toward fully understanding the genetic and biological complexity of each individual around the world who has Parkinson’s disease,” said Singleton. “Our hope is that results like these will provide researchers a road map for developing new genetic treatments and therapies for Parkinson’s disease.”

Reference: Rizig M, Bandres-Ciga S, Makarious MB, et al. Identification of genetic risk loci and causal insights associated with Parkinson’s disease in African and African admixed populations: A genome-wide association study. Lancet Neurol. 2023. doi: 10.1016/S1474-4422(23)00283-1

This article is a rework of a press release issued by the National Institute on Aging. Material has been edited for length and content.