Global Consortium Probes Genetics of Parkinson’s Disease in Latinos

The identification of gene variants that cause or lead to Parkinson’s disease (PD) has revolutionized research into the neurodegenerative disorder by identifying novel targets for the development of precision treatments. However, the vast majority of these studies have been conducted in populations of European or Asian ancestry. No large-scale PD genetic studies have ever been conducted in Latino populations.

Without such studies, millions of Latinos may never know the benefits of advancements in precision medicine. But now, an international genetic research collaboration headed by Ignacio Mata, PhD, of Cleveland Clinic’s Genomic Medicine Institute, seeks to identify new susceptibility genes in Latinos and sequence known causal genes in familial forms of PD to identify novel causal variants.

In collaboration with investigators from 12 institutions in multiple South American nations, Dr. Mata established the Latin American Research Consortium on the Genetics of Parkinson’s Disease (LARGE-PD). He hopes that LARGE-PD, the world’s largest PD case-control cohort of Latinos (more than 2,000 patients with PD and 2,000 healthy controls), will improve understanding of general and PD-related characteristics of Latinos and ensure that this population can access precision medicine-era treatments for PD.

“If we don’t learn more about common risk variants in this population,” Dr. Mata explains, “we won’t be able to offer Latinos the right care, useful genetic counseling and testing services, or opportunities to enroll in future precision medicine clinical trials.”

More than 10 million people worldwide are estimated to be living with PD. Although PD affects people of all races, certain races and ethnicities appear to be more affected than others. In one U.S. study, after adjusting for age and gender, the incidence rate per 100,000 was highest among Hispanics (16.6; 95% confidence interval [CI], 12.0-21.3), followed by non-Hispanic whites (13.6; 95% CI, 11.5-15.7), Asians (11.3; 95% CI, 7.2-15.3) and blacks (10.2; 95% CI, 6.4-14.0).

While genetic research in PD has revealed at least eight causal genes (SNCA, PARK2, PINK1, DJ-1, LRRK2, VPS35, DNAJC13 and RAB39B) and 30 susceptibility variants (e.g., GBA), the importance of these genes in PD in Latinos remains unknown.

Interestingly, Dr. Mata and others have shown that some of these variants are very rare or absent in Latinos, which means there may be novel variants or genes involved in the development of PD in this population. Dr. Mata is currently using novel genotyping and analytics to explore data from the LARGE-PD cohort to better understand the role of known causal and susceptibility variants. His team also seeks to identify novel causal variants by studying families in which no causal variant was found in genes known to cause PD.

“We’re confident that our study, and others like it, will reduce existing health disparities by enabling Latinos to be active participants in clinical trials of novel treatments designed to protect and/or treat individuals with specific genetic variants, making so-called personalized medicine a reality for this population,” Dr. Mata observes.