Research News

Ignacio Mata, PhD, Genomic Medicine, has received a five-year, $3.1 million grant from the National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health, to identify novel genes associated with Parkinson's disease (PD) in Latino populations.

Identification of genes that cause or increase the risk for PD has enabled better prediction of at-risk individuals and has pinpointed novel targets for precision treatments. However, because the majority of studies have been conducted in European or Asian populations, little is known about the genetics of PD in Latino populations, which means millions of individuals may never benefit from advancements in personalized medicine.

To address this disparity, Dr. Mata partnered with investigators from multiple Latin American institutions to establish the Latin American Research Consortium on the Genetics of Parkinson's Disease (LARGE-PD), the world's largest PD case-control cohort of Latinos. "The Parkinson's genes that we know about only explain a small proportion of the disease's heritability," said Dr. Mata. "There are additional novel genes awaiting discovery, and we believe that we will have the highest likelihood of success in finding those genes if we look at understudied populations, such as those from Latin America."

LARGE-PD currently includes 3,857 participants (about half of them with the disease), with a target to include at least 8,000 individuals by 2021 thanks to support from The Michael J. Fox Foundation, thus serving as a unique resource for genetic analysis in Latinos. Preliminary results in a small subset of LARGE-PD participants (N=1,500) already identified several novel candidate loci (location of a particular gene or genetic marker on a chromosome) for PD. As LARGE-PD has progressed, several multiplex PD families (with three or more affected individuals) have been identified and enrolled, and a preliminary study has shown that about 75% of them do not carry a mutation in a known gene, making them good candidates to screen for novel genes.

With this new award, Dr. Mata and collaborators will investigate genetic variants associated with PD in Latinos on a much larger scale, including the first ever trans-ethnic genome-wide association study (a research method that uses the power of genetic diversity to identify novel genes as well as fine-map those already known to identify the key variants) in collaboration with the largest consortium of European, Asian and African PD patients (the International Parkinson's Disease Consortium). In collaboration with a research group led by Dennis Lal, PhD, also in Genomic Medicine, they will then harness their data to develop and validate a Latino-specific polygenic risk score, which will indicate an individual's overall genetic risk of developing PD.

"Our data will improve our understanding of the biological causes of Parkinson's disease for all patients, regardless of their ethnicity. We also will find new therapeutic targets for treatment and improve diagnosis and risk prediction for individuals in Latin America as well as other countries with a growing Latino population, such as the United States," said Dr. Mata. "Our study, and others like it, will reduce existing health disparities by allowing Latinos to actively participate in clinical trials and receive personalized treatment based on their specific genetic variants."

This award includes collaboration with scientists in 11 countries: Peru: Instituto Nacional de Ciencias Neurológicas (Lima) (with their collaborating site at Universidad del Altiplano (Puno)); Brazil: Brazilian PD Consortium (CBPD) including, Universidade de São Paulo-Facultad de Medicina de Ribeirão Preto (Ribeirão Preto), Santa Casa de Misericórdia de Porto Alegre (Porto Alegre), Universidade Federal de Ciências da Saúde de Porto Alegre (Porto Alegre), Universidade Federal do Rio Grande do Norte (Natal), Universidade Federal de Goiás (Goiania), Universidade Federal de São Paulo (São Paulo), Universidade de São Paulo (São Paulo), Hospital e Maternidade Celso Pierro (São Paulo), Hospital Sírio-Libanês (São Paulo), Universidade Federal de Minas Gerais (Belo Horizonte), Universidade Federal do Paraná (Curitiba), Universidade de Campinas (Campinas), Universidade do Estado do Amazonas (Manaus), Hospital Ophir Loyola (Belem), Hospital Universitário de Brasília (Brasília), Universidade Federal do Ceará (Fortaleza), Universidade Federal do Rio de Janeiro (Rio de Janeiro), Hospital Universitário Gafrée e Guinle (Rio de Janeiro); Colombia: Universidad de Antioquia (Medellin), Universidad Nacional de Colombia (Bogota) and Fundación Valle del Lili (Cali); Uruguay: Universidad de la República-Hospital de Clínicas (Montevideo); Argentina: Centro de Parkinson y transtornos de Movimiento and Instituto de Neurociencias de Buenos; Aires (Buenos Aires); Chile: Centro de Transtornos del Movimiento (CETRAM) and University of Chile (Santiago); Honduras: Hospital San Felipe (Tegucigalpa); Ecuador: Hospital Teodoro Maldonado (Guayaquil) and Hospital Luis Vernaza (Guayaquil); Costa Rica: University of Costa Rica (San jose); Mexico: TecSalud (Monterrey), Instituto Nacional de Neurología y Neurocirugía (Mexico City), Hospital General de México (Mexico City), ISSSTE Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado (Mexico City); and West Indies: St. George's University (St. George, Grenada).