Expanding the Genetic Pool of Non-European Populations in Parkinson Disease: Ignacio Mata, PhD

WATCH TIME: 5 minutes

"I would say about 95% of all studies that have been done until this date have included individuals of European ancestry. This paper was a proof-of-concept that increasing diversity can add a lot to what we know about the disease."

Genetics cause about 10% to 15% of all cases of Parkinson disease (PD). In some families, mutations in certain genes are inherited or passed down from generation to generation, with increasing levels of risk throughout different ancestral backgrounds. Although over 90 independent risk variants have been identified for PD using genome-wide association studies (GWAS), most studies have been performed in just 1 population at a time.

Several in the field believe that identification of genetic risk factors is imperative for mitigating the global burden of PD, one of the fastest growing age-related neurodegenerative diseases. Recently published in Nature, a large-scale, multi-ancestry meta-analysis of PD GWAS further looked at genetic influences across 4 ancestral populations: European, East Asian, Latin American, and African. Led by Ignacio Mata, PhD, the study included 49,049 cases, 18,785 proxy cases, and 2,458,063 controls of such individuals.

Results showed 78 independent genome-wide significant loci, including 12 potentially novel loci and fine-mapped 6 putative causal variants at 6 known PD loci. After combining the results with publicly available eQTL data, the researchers identified 25 putative risk genes in these novel loci whose expression was associated with PD risk. Mata, a recently appointed associate professor of neurology at the Cleveland Clinic Lerner Institute, sat down to discuss the reasons behind the meta-analysis and what the findings describe. He spoke on the significance of the data, how it expands the knowledge of genetics and PD, and why it’s important to continue to include patients of all backgrounds in subsequent studies.

REFERENCE
1. Kim JJ, Vitale D, Otani DV, et al. Multi-ancestry genome-wide association meta-analysis of Parkinson’s disease. Nature. 2024;56(27-36). doi:10.1038/s41588-023-01584-8