Cleveland Clinic researcher Ignacio Mata, PhD, has received a five-year, $3.1 million grant from the National Institute of Neurological Disorders and Stroke (NINDS) to identify novel genes associated with Parkinson disease (PD) in Latino populations.
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The funding will expand the work Dr. Mata has led 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 genes that we know about explain only a small proportion of the disease’s heritability,” says Dr. Mata, staff in Cleveland Clinic’s Genomic Medicine Institute. “There are additional novel genes awaiting discovery, and we believe we will have the highest likelihood of success in finding those genes if we look at understudied populations, such as those from Latin America.”
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 most PD studies have been conducted in European or Asian populations, little is known about the genetics of PD in Latino populations, leaving millions of individuals less likely to benefit from advancements in personalized medicine.
To address this disparity, Dr. Mata partnered with his collaborators from Latin America to establish LARGE-PD as a unique resource for genetic analysis in Latinos. LARGE-PD, which currently includes 3,857 participants (about half of whom have PD), aims to include at least 8,000 individuals by 2021 with support from The Michael J. Fox Foundation.
Preliminary results in a subset of LARGE-PD participants (n = 1,500) already identified several novel candidate loci for PD. As LARGE-PD has progressed, several multiplex PD families (i.e., 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 NINDS award, Dr. Mata and collaborators will investigate genetic variants associated with PD in Latinos on a much larger scale, including the first-ever transethnic genome-wide association study (GWAS) in collaboration with the International Parkinson Disease Genomics Consortium, the largest consortium of patients of European, Asian and African ancestry. In collaboration with a research group led by Dennis Lal, PhD, also of Cleveland Clinic’s Genomic Medicine Institute, they plan to 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 PD for all patients, regardless of their ethnicity,” says Dr. Mata. “We also will find new therapeutic targets and improve diagnosis and risk prediction for individuals in Latin America and other countries with a growing Latino population, such as the United States. 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.”
The NINDS award includes collaboration with scientists in 11 other nations: