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Characterizing the Genetic Architecture of Parkinson’s Disease in Latinos

To address the lack of diversity in Parkinson’s disease genetic research, Dr. Mata and colleagues conducted the first ever genome-wide association study of Latino Parkinson’s disease patients from South America.


An international research team led by Cleveland Clinic has presented the most comprehensive characterization of the underlying genetic basis for Parkinson’s disease (PD) in Latinos to date, marking an important step towards more inclusive PD genetic research.

“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,” said Ignacio Mata, PhD, assistant staff in the Genomic Medicine Institute and lead author on 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.”

In this study, published in Annals of Neurology, Dr. Mata and international collaborators performed the first ever genome-wide association study (GWAS) of Latino PD patients from South America. Their analysis relied on patient data from the world’s largest PD case-control cohort of Latinos, called the Latin American Research Consortium on the Genetics of Parkinson’s Disease (LARGE-PD), which includes individuals from 35 institutions in 12 countries across Latin America and the Caribbean.

Conducting the first-ever genome-wide association study in Latinos

The researchers scanned the genomes of 1,497 individuals (807 PD cases; 690 healthy controls) from nine LARGE-PD sites in five countries (Uruguay, Brazil, Colombia, Peru and Chile) to investigate genetic variations associated with PD.

Notably, they demonstrated that SNCA, a gene previously linked to PD in European and East Asian populations, had genome-wide significance in the LARGE-PD cohort and a replication cohort, indicating its critical role in PD etiology in Latinos. In addition, they identified the novel gene NRROS as a biologically plausible PD risk gene, particularly in individuals from Peru, but indicated that further studies are needed to validate this finding.

The researchers then assessed the significance of PD variants previously identified in European and East Asian populations for the LARGE-PD cohort, and found a substantial overlap of PD genetic architecture between Europeans and Latinos. They also explored the relationship between PD risk and Latino population ancestry, which tends to have a three-way admixture pattern with contributions from African, European and Native American ancestry, and pinpointed variants associated with African and Native American ancestries that may influence PD 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,” Dr. Mata said. “PD is a global disease, so it is crucial that genetic studies reflect the wide diversity of patients with PD.”

Next steps for LARGE-PD

Dr. Mata and his colleagues established LARGE-PD in 2009 with funding from the Parkinson’s Foundation to increase diversity in PD genetics studies and better understand the genetics of PD in Latinos. They recently conducted the first ever analysis of copy number variants (CNVs), or large structural genetic changes involving the deletion and/or duplication of DNA segments, in Latino PD patients. The study, published in Movement Disorders, demonstrated that CNVs in known PD genes are associated with PD in Latino populations. Specifically, they found that Latino patients with PD were more likely than controls to carry CNVs affecting known PD genes, and these patients often experienced a significantly earlier onset of symptoms.

“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,” said Dr. Mata. “In the next few years, we plan to triple our cohort with funding from the Michael J. Fox Foundation, which will allow us to replicate our results and increase our power to identify new genetic associations. We also will work with the Aligning Science Across Parkinson's Global Parkinson's Genetics Program to perform the largest and most diverse genetic study of PD, with the goal of including 150,000 individuals, of which at least 50,000 will be from underrepresented populations.”

Douglas Loesch, graduate student in the Institute for Genome Sciences at the University of Maryland School Of Medicine, is first author of this study, which was supported in part by the Parkinson’s Foundation, the American Parkinson’s Disease Association, Universidad de Antioquia and the National Heart, Lung, and Blood Institute of the National Institutes of Health.

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