Global Consortium Identifies Novel Parkinson's Genetic Risk Factor in African Populations

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• Cross-cohort analysis found novel variant in GBA1 gene associated with higher risk of Parkinson's in people of African ancestry
• Finding is from Nigerian and U.S. cohorts contributing to the Global Parkinson's Genetics Program (GP2), a global effort to deepen understanding of Parkinson's disease genetics, including in populations traditionally underrepresented in research
• Cohorts and consortium enabled by support from Aligning Science Across Parkinson's (ASAP) initiative and The Michael J. Fox Foundation for Parkinson's Research (MJFF)
• Implications for therapies already in human testing targeting the GBA1 pathway and potential for novel treatment approaches

NEW YORK, Aug. 24, 2023 /PRNewswire/ -- Timed to the publishing of a paper in The Lancet Neurology, The Global Parkinson's Genetics Program (GP2) announces the discovery of a genetic variant that increases risk of Parkinson's disease (PD) in people of African and African admixed populations — a first that may revolutionize treatment for this underserved population and that is a testament to the need for and impact of an international approach to genetic research. The variant on the GBA1 gene was identified by GP2 researchers, led by those at the U.S. National Institutes of Health (NIH), the University of Lagos in Nigeria, and University College London (UCL). GP2 is a resource program of the Aligning Science Across Parkinson's (ASAP) initiative that is funded by the Sergey Brin Family Foundation and implemented by The Michael J. Fox Foundation for Parkinson's Research (MJFF).

"This is an historic discovery and the first realization of our goal with GP2 — to provide a comprehensive understanding of the genetic architecture of Parkinson's disease — which necessitates the inclusion of populations traditionally underrepresented in research," said Ekemini Riley, PhD, ASAP managing director. "GP2 has significantly advanced the practice of thoughtfully bringing together data across cohorts, countries and continents in a way that has led to this major breakthrough, will continue to accelerate discovery, and lay the groundwork for new therapies to improve the lives of people living with the disease. We thank the participants for sharing their biology, GP2's principal investigators for their vision, and the research community for their commitment to open science."

The discovery of a novel GBA1 variant came from a comprehensive first-of-its-kind genome-wide assessment led by GP2 in 1,488 people with PD and 196,430 control volunteers of African and African admixed ancestry. Most participants were part of (i) the Nigerian Parkinson Disease Research Network, (ii) the U.S.-based Black and African American Connections to Parkinson's Disease (BLAAC PD) study, (iii) the 23andMe research community. Analysis of genomic data was led by scientists at the NIH's Center for Alzheimer's and Related Dementias. Other GP2-linked cohorts contributed as well.

• The Nigerian Parkinson Disease Research Network is part of the International Parkinson's Disease Genomics Consortium (IPDGC) Africa, a collaboration of cohorts across 12 countries to increase the scientific understanding of Parkinson's disease in Africans. IPDGC Africa is funded in part by MJFF.
• BLAAC PD is a cross-sectional study collecting a blood or saliva sample and clinical data from Black and African Americans. The BLAAC PD study recently expanded to six sites in the U.S.; it is funded by ASAP and implemented by MJFF.
• Most participants came from the sizable cohort personal genetics company 23andMe has assembled comprising people who have consented to contribute their data for use in varied research studies.

"Genetics study in people of European descent has led to a wave of treatment approaches in development," said Mie Rizig, MD, co-first author of The Lancet Neurology paper, Lead Coordinator of IPDGC Africa and a Senior Clinical Research Fellow at UCL. "It has been our hope in organizing genetic data from African populations, and in contributing to complementary datasets with GP2, that findings would indicate those therapies have broader application or would illuminate novel targets for a next generation of strategies."

GP2 Builds Value of Prior Investments in Global Genetics Research

GP2 gathers and analyzes global data and samples from existing cohorts — Parkinson's and control volunteers — then makes its data available worldwide for additional studies of Parkinson's genetics. The program is partnering with more than 140 cohorts across 58 locations.

"As researchers and clinicians, our shared responsibility is to make sure Parkinson's science is representative of all communities around the world," said Njideka Okubadejo, MD, Professor of Neurology at the University of Lagos, College of Medicine. "This GBA1 result is a step toward that future, where the research field is prioritizing, learning from, and treating all people with Parkinson's disease."  

ASAP launched GP2 in 2019, building on previous funding efforts from MJFF to expand global genetics study in populations traditionally underrepresented in research. As early as 2004 The Michael J. Fox Foundation supported the Edmond J. Safra Global Genetics Consortia to generate and share genetics data in varied international populations. Today, GP2 is partnering with over 140 cohorts from around the world, assembling, generating and sharing data to uncover novel insights and similarities.

"The field of Parkinson's has made leaps of progress in recent decades. That work has been built upon scientific discoveries — like this one — and fueled by research participants and scientists," said Sohini Chowdhury, MJFF's chief program officer. "Our work can be exponentially successful if we ensure that our research efforts are inclusive of everyone impacted by this disease. The Foundation and our partners are committed to this work because it is vital to realizing our shared mission of ending Parkinson's."

New Variant May Broaden Application of Therapies Already in Testing

While more research is needed to define the exact mechanism of the new variant, initial findings suggest that like prior mutations in GBA1, this variant results in lowered activity of the glucocerebrosidase (GCase) enzyme.

As previously discovered GBA1 variants have been linked to increased risk of Parkinson's disease — most notably in people of Ashkenazi Jewish descent — multiple therapies to increase GCase activity, with varied therapeutic approaches, already are in clinical trials. With further research, the identification of this new GBA1 variant could mean that more people benefit from those treatments.

Researchers can obtain data from the study by accessing the Accelerating Medicines Partnership® (AMP®) program platform, a public-private partnership among the NIH, multiple biopharmaceutical and life sciences companies, and non-profit organizations. MJFF and ASAP are partners in the AMP Parkinson's disease (AMP PD) program.

"I'm proud to be a part of this," said Dionne Phillips of Chicago, Illinois, a BLAAC PD study volunteer at the University of Chicago who was diagnosed at age 39. "Everyone asks themselves, 'Why?' when they hear that diagnosis. I'm glad we may now have a partial answer and thrilled that it may mean there could be a way to stop it."

About Aligning Science Across Parkinson's Disease (ASAP)
The Aligning Science Across Parkinson's (ASAP) initiative is a coordinated research initiative to advance targeted basic research for Parkinson's disease. ASAP is devoted to accelerating the pace of discovery and informing the path to a cure for Parkinson's disease through collaboration, research-enabling resources, and data sharing. Led by Nobel Laureate Dr. Randy Schekman and Dr. Ekemini Riley, ASAP is managed by the Coalition for Aligning Science and is working with The Michael J. Fox Foundation to implement its programs. The initiative was incubated at the Milken Institute Center for Strategic Philanthropy with support from the Sergey Brin Family Foundation. For more information, visit us at www.parkinsonsroadmap.org and Twitter. 

About The Michael J. Fox Foundation for Parkinson's Research (MJFF) 
As the world's largest nonprofit funder of Parkinson's research, The Michael J. Fox Foundation is dedicated to accelerating a cure for Parkinson's disease and improved therapies for those living with the condition today. The Foundation pursues its goals through an aggressively funded, highly targeted research program coupled with active global engagement of scientists, Parkinson's patients, business leaders, clinical trial participants, donors and volunteers. In addition to funding $1.75 billion in research to date, the Foundation has fundamentally altered the trajectory of progress toward a cure. Operating at the hub of worldwide Parkinson's research, the Foundation forges groundbreaking collaborations with industry leaders, academic scientists and government research funders; creates a robust open-access data set and biosample library to speed scientific breakthroughs and treatment with its landmark clinical study, PPMI; increases the flow of participants into Parkinson's disease clinical trials with its online tool, Fox Trial Finder; promotes Parkinson's awareness through high-profile advocacy, events and outreach; and coordinates the grassroots involvement of thousands of Team Fox members around the world. For more information, visit us at www.michaeljfox.org, Facebook or Twitter.