Study Rationale

A substantial proportion of risk for Parkinson’s disease (PD) is driven by genetics, and genetic links to PD have advanced disease understanding and therapeutic development. There is still much to learn about identified genetic risk factors, as so much remains undiscovered. We know that not all people with PD-linked mutations develop the disease, and, in those who do, onset can be late in life, suggesting existence of protective genetic factors that prevent or delay disease. The path to further understanding the genetic architecture of PD requires working collaboratively to analyze samples from hundreds of thousands of people representing diverse backgrounds and disease experiences. Progress requires working openly and sharing data, processes, and results.

Aligning Science Against Parkinson’s (ASAP) has developed a strategic roadmap to collectively tackle field-wide challenges. Its three-part strategy aims to support meaningful, multidisciplinary collaboration; generate research-enabling resources; and democratize data. ASAP supports the Global Parkinson’s Genetics Program (GP2) in service of those goals. The findings and compiled resources from this program will seed further discovery and validation toward new treatments for Parkinson’s disease.

Study Design

This study will engage existing global consortia and cohorts to expand genetic analysis efforts with samples from more than 150,000 people, including those with PD, people at risk for PD, and control volunteers. GP2 will use cutting-edge techniques to analyze samples from people around the world living in or with ancestors from Africa, Asia, Europe, and Central and South America. These efforts will transform understanding of the genetic architecture of PD across populations, including those currently underserved in research. The resulting data will aim to provide new biological understanding, greater genetic resolution, better disease risk profiles, and data-driven insight into the full spectrum of PD.

Additionally, GP2 will study rare familial forms of PD with detailed gene discovery efforts toward identification of novel disease-causing mutations.

Lastly, GP2 aims to democratize these efforts. There will be significant focus on training the future generation of genetic researchers and clinicians. The underlying data, analytical processes, and results from GP2 will be made available to the larger research community as quickly as possible, with minimum barriers to access and use.

Impact on Diagnosis & Treatment of Parkinson’s Disease

Expanded understanding of the genetic architecture of PD has wide and deep implications for research and care. Findings and data generated from GP2 — new PD-linked genetic associations, relationships between mutations, protective variants, commonalities, and differences in the genetics of disease in individuals of diverse ancestry — can help investigators understand who may develop PD, at what time, and to what degree. They can point scientists to new targets against which to develop new treatments to slow, stop, or prevent PD disease progression. They can help study sponsors design smaller, faster trials with the right drug for the right person at the right time with better methods to assess efficacy. And they can help people living with Parkinson’s and their families understand risk, make lifestyle changes to delay onset, and develop a treatment plan.

Steering Committee

GP2 is a five-year study led by Andrew Singleton, PhD, of the National Institutes of Health and a steering committee comprising:

• Cornelis Blauwendraat, PhD
  National Institutes of Health, USA
• Alexis Brice, MD
  Brain and Spine Institute, France
• Ignacio Fernandez Mata, PhD
  Cleveland Clinic, USA
• Brian Fiske, PhD
  Michael J. Fox Foundation, USA
• Tatiana Foroud, PhD
  Indiana University, USA
• Thomas Gasser, MD
  University of Tubingen, Germany
• John Hardy, PhD
  University College London, United Kingdom
• Peter Heutink, PhD
  German Center for Neurodegenerative Diseases, Germany
• Christine Klein, MD
  University of Lubeck, Germany
• Rejko Kruger, MD
  University of Luxembourg, Luxembourg
• Ken Marek, MD
  Michael J. Fox Foundation, USA
• Huw Morris, FRCP, PhD
  University College London, United Kingdom
• Michael Nalls, PhD
  Data Tecnica International, USA
• Alastair Noyce, MRCP, PhD
  Queen Mary University of London, United Kingdom
• Alyssa Reimer, BA
  Michael J. Fox Foundation, USA
• Ekemini A. U. Riley, PhD
  Milken Institute Center for Strategic Philanthropy, USA
• Luba Smolensky, MS
  Michael J. Fox Foundation, USA
• Enza Maria Valente, MD, PhD
  University of Pavia, Italy
• Nigel Williams, PhD
  Cardiff University, United Kingdom
• Nicholas Wood, MB ChB, PhD
  University College London, United Kingdom

ASAP is leveraging The Michael J. Fox Foundation’s grantmaking infrastructure to give awards to various partners for this study. Those with existing potential partner cohorts can email grants@parkinsonsroadmap.org.