Study Examines Genetics of Parkinson’s in Latinos

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by Marisa Wexler |

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Latinos and Parkinson's

Genetic variations in the gene SNCA are tied to an increased risk of Parkinson’s disease (PD) among Latinos, according to a recent analysis. Also, Latinos with African ancestry are less likely to develop Parkinson’s.

The analysis is “the most comprehensive examination of PD genetics in this population [Latinos] to date,” according to the researchers.

The results were published in Annals of Neurology, in the study, “Characterizing the Genetic Architecture of Parkinson’s Disease in Latinos.”

It is well-established that certain genetic factors can increase an individual’s risk of developing Parkinson’s. To date, however, there has been little representation of Latinos in research about the genetics of Parkinson’s.

“PD impacts all ethnic groups, but since genetic studies have largely been limited to individuals of European and East Asian ancestry, little is known about the genetic architecture of PD in Latino populations,” Ignacio Mata, PhD, said in a press release. Mata is on staff at the Genomic Medicine Institute and co-author of the study.

“As we see PD incidence rates rise in nearly every global region, the importance of greater diversity in PD research cannot be overlooked,” Mata said.

Researchers collected genetic data on 1,497 people — 807 with Parkinson’s and 690 without — from nine clinical sites in five Latin American countries (Uruguay, Brazil, Colombia, Peru and Chile). These sites are part of the Latin American Research Consortium on the Genetics of Parkinson’s Disease (LARGE-PD), an ongoing study investigating the genetics of Parkinson’s in Latino populations.

The team then conducted a genome-wide association study, or GWAS. This  kind of analysis basically involves looking for specific genetic variants that are more common in people with Parkinson’s than in those without.

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The team found that variations in the gene SNCA — that which enables the production of the alpha-synuclein protein that accumulates in toxic clumps inside nerve cells of those with Parkinson’s — were associated significantly with Parkinson’s risk. This gene also has been tied to Parkinson’s in previous studies of European populations. A separate analysis using data from the company 23andMe also showed a significant link between SCNA variations and Parkinson’s risk.

The researchers also looked at whether dozens of other genetic variants that have been tied to Parkinson’s in prior studies in Europeans showed similar effects among Latinos. Overall, 63 of 76 variants (82.9%) showed similar Parkinson’s associations in the Latino group as in other studies, which suggests there is “a substantial overlap in the genetic architecture of PD
between Latinos and Europeans,” the researchers wrote.

In the LARGE-PD population, most participants had European and/or Native American ancestry, with African ancestry accounting for most of the remainder. Most people in Latin America derive their genetic lineage from some combination of these three origins.

The researchers conducted admixture analyses, essentially looking for differences in Parkinson’s risk based on ancestry. They found that people with African ancestry were less likely overall to develop Parkinson’s, which was tied to variations in a gene called RPS6KA2 that were common among people with this ancestry.

The admixture analysis also showed that the gene STXBP6 was particularly common in people with Native American ancestry. Also of note, in the original GWAS, variations in the gene NRROS showed some evidence of an association with Parkinson’s, especially among people with Native American ancestry.

The researchers stressed a need for further studies to characterize the genetics of Parkinson’s disease among Latinos, noting in particular a need to include more representation of people with Native American ancestry. They said that the current analysis was limited by its size, which was too small to reliably detect genetic variants that are comparatively rare, or have a less-profound effect on Parkinson’s risk.

“As we continue our work to gain comprehensive understanding of population-specific PD genetic architecture in Latino populations, inclusion of Latino PD patients from diverse ancestral backgrounds, such as those with significant Native American or African ancestries, is a necessity. PD is a global disease, so it is crucial that genetic studies reflect the wide diversity of patients with PD,” Mata said.

Last year, Mata and colleagues published another analysis of data from LARGE-PD, which looked at the effect of a specific type of mutation called a copy number variation (CNV), which is when a piece of DNA gets erroneously copied or deleted. They found that CNVs in known Parkinson’s genes are associated with the disease in Latino populations.

“The global collaboration and support that has made LARGE-PD possible have enabled us to make tremendous strides towards increasing diversity in genetic studies and minimizing health disparities in underrepresented populations, and we are continuing to charge forward,” Mata said, adding that the study plans to expand substantially in the next several years.

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