Understanding monogenic Parkinson's disease at a global scale

Area of Science:

• Genetics
• Neurology
• Epidemiology

Background:

• Previous monogenic Parkinson's disease (PD) research predominantly focused on European/White populations, limiting global genotype-phenotype insights.
• Limited diversity in PD genetic studies restricts understanding of disease mechanisms and therapeutic targets across different ancestries.

Approach:

• Combined the Michael J. Fox Foundation Global Monogenic PD (MJFF GMPD) Project and the Global Parkinson’s Genetics Program (GP2) Monogenic Network.
• Developed a sustainable infrastructure to build a global monogenic PD cohort, including underrepresented PD centers.
• Integrated data from existing publications and newly identified patient cohorts.

Key Points:

• Successfully merged two major global efforts to create a comprehensive monogenic PD cohort.
• Established a sustainable infrastructure for ongoing global research in monogenic PD.
• Enabled the identification of the multi-ancestry spectrum of monogenic PD.

Conclusions:

• Team science approaches are crucial for generating globally relevant and comprehensive results in complex diseases like PD.
• This merged cohort and infrastructure will facilitate future studies on factors modifying PD penetrance and expression.
• Future research should prioritize multi-ancestry studies to fully understand PD genetics and improve patient outcomes.