Understanding monogenic Parkinson's disease at a global scale

Abstract

Until recently, about three-quarters of all monogenic Parkinson's disease (PD) studies were performed in European/White ancestry, thereby severely limiting our insights into genotype-phenotype relationships at global scale. The first systematic approach to embrace monogenic PD worldwide, The Michael J. Fox Foundation Global Monogenic PD (MJFF GMPD) Project, contacted authors of publications reporting individuals carrying pathogenic variants in known PD-causing genes. In contrast, the Global Parkinson's Genetics Program's (GP2) Monogenic Network took a different approach by targeting PD centers not yet represented in the medical literature. Here, we describe combining both efforts in a "merger project" resulting in a global monogenic PD cohort with build-up of a sustainable infrastructure to identify the multi-ancestry spectrum of monogenic PD and enable studies of factors modifying penetrance and expression of monogenic PD. This effort demonstrates the value of future research based on team science approaches to generate comprehensive and globally relevant results.

Figure 1:. World map of centers participating in the GP2 MN and the MJFF GMPD project

Colored are the countries from which one or more centers participated in the MJFF GMPD project and GP2 MN (blue) or only in GP2 MN (green). Colored in purple are new centers in underrepresented countries that were recruited based on the new approach of GP2 MN. Blue: Argentina, Australia, Austria, Belgium, Canada, Denmark, France, Germany, Greece, Hungary, Israel, Italy, Japan, Luxembourg, Malaysia, Netherlands, Norway, Poland, Portugal, Saudi Arabia, Singapore, Slovakia, South Africa, South Korea, Spain, Sweden, Taiwan, Thailand, Turkey, UK, USA Green: Chile, Czechia, New Zealand, Switzerland Purple: Bangladesh, Colombia, Indonesia, Iran, Mongolia, Nepal, Nigeria, Pakistan, Philippines, Sri Lanka, Tunisia