By Ignacio F. Mata, Ph.D.
There is no question that since the human genome was fully sequenced in 2003, genetic studies have allowed huge advances in the understanding of complex diseases. These studies have identified many genes that harbor both causal and risk-modifying variants, which has improved our understanding of a wide variety of disorders. However, a major shortcoming of this work is the limited diversity of the study populations. By 2016 the overall proportion of non-European derived participants in large genetic studies was only 19%, and representation from some groups such as Latinos remained below 1%. This Euro-centric approach will without a doubt widen disparities in research and health.
Unfortunately, these patterns also hold true for genetic studies of Parkinson’s disease (PD) where inclusion of Latinos has been and remains particularly low, despite the fact that the risk for developing the disease has been suggested to be elevated in Latinos living in the US. To address this lack of diversity and understand the risk factors that may be increasing the risk of PD in Latinos we have, over the past decade, created the Latin American Research Consortium on the Genetics of PD (LARGE-PD). LARGE-PD is a rapidly-expanding collaboration between our group in Seattle and investigators currently at nine institutions in six countries across South America (Argentina, Brazil, Colombia, Ecuador, Peru and Uruguay). Each site uses uniform diagnostic criteria and collects a standardized set of clinical and demographic variables. The initial goal of the project was to generate the first large PD case-control sample of Latinos. Thanks to funding from the Parkinson’s Disease Foundation to date we have enrolled nearly 4,000 individuals. This cohort provides a unique resource for genetic analysis in previously understudied populations.
We have started to study this cohort and what we have seen so far is that some of the most common PD-associated variants discovered in populations of European origin occur at a substantially lower frequency in Latin America and there are novel variants in those same genes that are common in patients from certain populations in these countries. Thus the genetic architecture of PD might differ between Latinos and other population groups. The same have been shown in several other diseases including cancer and asthma. This also suggests that new PD-related genes could be “hiding” in PD patients of non-European origin and their study will provide new pieces that may increase our knowledge about the causes of this complex disorder.
In the next three years, and thanks to a new grant from the PDF, we will be performing the first large-scale PD genetic study in Latinos to date. This study will help identify population specific genetic risk factors in Latinos. We will be also studying several large families from LARGE-PD to try to identify new genes, thus “new players” that may help shaping the neurodegenerative process occurring in all patients with PD. In order to replicate our results from Latino America we have also begun to recruit a Latino PD case-control sample here in the US in collaboration with several movement disorder centers, as well as patient support centers and foundations, across the country.
I believe that failure to improve the inclusiveness of future studies could have several negative consequences for Latinos. For example, not knowing the genetic profile of PD in Latinos will limit the utility of clinical genetic tests and will restrict the use of genetic information to tailor current and new treatments as part of the so-called precision or personalized medicine.
Ignacio F. Mata, Ph.D., presented two posters at the 4th World Parkinson Congress including one at the Hot Topics session. He is an Acting Assistant Professor of Neurology at the University of Washington and Research Biologist at the Geriatric Education and Clinical Center within the VA Puget Sound Health Care System (Seattle, WA)
To find out more on how you can participate in his study, click on the images above.
Ideas and opinions expressed in this post reflect that of the authors solely. They do not reflect the opinions or positions of the World Parkinson Coalition®.