Every ethnic group across the globe is impacted by Parkinson’s disease (PD). However, most of the PD genetic information that is studied by scientists has primarily been collected from people of European and East Asian ancestry. In fact, as of 2018, only 1.3% of study participants in the genome-wide association study (GWAS) Catalog data are Latino. With Parkinson’s on the rise on a global scale, the importance of increasing the genetic diversity of research participants is of utmost importance.
What’s the difference between Hispanic, Latino and Latinx?
- Hispanic refers to people from Spanish-speaking countries.
- Latino/Latina refers to people who descended from Latin America.
- Latinx is a gender-neutral term for a person of Latin descent.
A recently published study in the Annals of Neurology, titled “Characterizing the Genetic Architecture of Parkinson's Disease in Latinos” (Loesch et al., 2021) sought to address this lack of diversity in PD genetic research.
The senior author of this study, Ignacio Mata, PhD, is from the Cleveland Clinic Lerner College of Medicine, a Parkinson’s Foundation Center of Excellence. Dr. Mata serves as an advisor to the Parkinson’s Foundation’s Hispanic and Latino efforts and is a Stanley Fahn Junior Faculty Award recipient.
Dr. Mata and colleagues performed the first-ever genome-wide association study (GWAS) of Latinos with PD in South America. GWAS is an approach used to identify associations between genetic variants and risk for particular diseases.
“There are many reasons this study gives me hope for Parkinson’s research,” Dr. Mata said. “We want to make sure the progress we are achieving in understanding the role of genetics in PD is applicable to all individuals, and right now that is not possible because of our Euro-centric research, however, this research is making a little dent on that front for the Latino community.”
Dr. Mata’s team utilized the data from the Latin American Research Consortium on the Genetics of Parkinson’s Disease (LARGE-PD) — the world’s largest PD case-control group of Latinos. They then scanned for 8.7 million DNA variants using a genotyping array (a test that checks for changes in specific areas of a person’s chromosomes). After a careful quality control process, the genetics of 1,497 people (807 participants with and 690 without PD) from Uruguay, Brazil, Colombia, Peru, and Chile were included.
The participants with PD consisted of 53% men, with an average age of 61.7 years, and an average age of PD onset of 54.1 years. The group without PD consisted of 33% men with an average age of 56.5 years. Participant numbers are reflective of the fact that Parkinson’s affects more men than women.
Additionally, as the gold standard of GWAS studies requires independent evidence that genetic study findings are reliable, a group of 1,234 Latinos with self-reported PD and 439,522 people without PD were tested for genetic variants by the consumer genetics and ancestry company, 23andMe. Researchers also utilized genetic admixture (when people from genetically distinguishable groups have children together) analyses, which uses DNA to help determine ancestry. In this case, Latino populations tend to have a three-way DNA admixture of African, European, and Native American ancestry.
- The role of the SNCA gene (a common Parkinson’s gene mutation) in the development of PD in the Latino population is substantial. In both the LARGE-PD group and the replication group of 23andMe, only the Synuclein Alpha (SNCA gene) was found to have genome-wide significance in the GWAS.
- Of note, the SNCA gene, which produces the protein alpha-synuclein, is associated with familial PD, and has been previously linked to PD in people of European and East Asian descent.
- Variants near the NRROS gene approached genome-wide significance but were not replicated in 23andMe.
- NRROS findings were prominent in Peruvians of primarily Amerindian ancestry.
- NRROS is biologically possible as a potential PD risk gene, as NRROS knockout mice display neurological abnormalities including defects in motor functions.
- In the admixture analyses, there was evidence that having African ancestry was protective against PD risk, which appeared to be associated with the RPS6KA2 gene.
What Does It Mean?
Genetics cause between 10% to 15% of all Parkinson’s disease. In some families, genetic changes (or mutations) are inherited or are passed down from generation to generation. Scientists have identified certain groups of genes that are known to be associated with family-linked Parkinson’s, including the genes SNCA, PRKN and DJ-1. Genetic research has made great strides to help scientists better understand the biology of Parkinson's and guide the development of treatments for all people with PD.
This study is groundbreaking: this is the most comprehensive examination of PD genetics throughout South America increasing the diversity in PD genome-wide association (GWAS) data in PD.
Of note in the study findings, the SNCA gene, which produces alpha-synuclein, was found to be clinically significant in the Latino population. This confirms that there is substantial overlap in the genetics of PD in Latinos as comparable to those of European-ancestry and warrants further study.
The NRROS gene, which is known for being associated with problems in motor functions and is critical for the development of microglia (immune cells of the brain responsible for maintenance of brain tissue) is another key finding, despite it not being replicated in 23andMe. The difference in findings may be because of the higher proportion of Native American ancestry present in the LARGE-PD group compared with the 23andMe group (47% vs. 19%), thus replication in another independent group with high Native American ancestry is needed.
Additionally, the authors found several other regions of potential significance that could not be confirmed with certainty because of the limited number of participants in this study. In short, this is an excellent first step towards proactively addressing the lack of diversity in Parkinson’s disease genetic research. Additional studies with even larger number of Latino participants are needed to reliably uncover additional genetic causes. Diversity in research studies is essential for optimizing our understanding of PD and potential future treatments.
“Our results show that there is some overlap in the genetic architecture of PD between populations, although the variants involved may be slightly different,” said Dr. Mata. “However, we need larger cohorts to really identify those population-specific components. We are working on more than doubling LARGE-PD in the next two years to help with this effort.”
The Parkinson’s Foundation believes in diversifying research, which is why its PD GENEration: Mapping the Future of Parkinson’s Disease is conducted in English and Spanish. Help further Parkinson’s research by enrolling today in English or Spanish.
The Parkinson’s Foundation believes in empowering the Parkinson’s community through education. Learn more about genetics and Parkinson’s by visiting the below Parkinson’s Foundation resources, or by calling our free Helpline at 1-800-4PD-INFO (1-800-473-4636).
- PD GENEration: Mapping the Future of Parkinson’s Disease
- Common Genetic Mutations
- Parkinson’s and the Pan American Community
- Understanding Genetics
Spanish Resources: Genetics and Parkinson’s
- PD GENEration: Trazando el futuro de la enfermedad de Parkinson
- Episodio 6: La representación hispana en la comunidad del Parkinson
- Participando en la investigación
Loesch, D. P., Horimoto, A., Heilbron, K., Sarihan, E. I., Inca-Martinez, M., Mason, E., . . . Latin American Research Consortium on the Genetics of Parkinson's, D. (2021). Characterizing the Genetic Architecture of Parkinson's Disease in Latinos. Ann Neurol. doi:10.1002/ana.26153
Zhang, Q. S., Heng, Y., Yuan, Y. H., & Chen, N. H. (2017). Pathological alpha-synuclein exacerbates the progression of Parkinson's disease through microglial activation. Toxicol Lett, 265, 30-37. doi:10.1016/j.toxlet.2016.11.002