Accelerating Medicines Partnership: Parkinson's Disease. Genetic Resource

Area of Science:

• Genomics and Computational Biology
• Neurodegenerative Diseases

Background:

• Whole-genome sequencing (WGS) data offer immense potential for disease discovery but require substantial computational resources and data harmonization.
• Integrating diverse WGS, RNA expression, and clinical data across multiple cohorts is crucial for increasing statistical power in Parkinson's disease (PD) research.

Purpose of the Study:

• To introduce the Accelerating Medicines Partnership Parkinson's Disease (AMP PD) program's research platform.
• To describe the initial release (Version 1) of harmonized WGS data from multiple PD cohorts.
• To provide a foundation for democratizing data access and analysis for the PD research community.

Main Methods:

• Development of a research platform integrating WGS, RNA expression, and clinical data.
• Harmonization of data from four distinct cohort studies.
• Joint genotyping of 3941 participants using the TOPMed Freeze 9 Variant Calling Pipeline for WGS data analysis.

Main Results:

• Version 1 includes WGS data from 3941 participants, comprising idiopathic PD patients, healthy controls, prodromal subjects, and genetically enriched cohorts.
• No significant enrichment of pathogenic variants was found in the idiopathic PD group.
• Higher polygenic risk scores were observed in PD participants across both genetically enriched and non-enriched cohorts, with a correlation between genetically enriched cohorts and Ashkenazi Jewish ancestry.

Conclusions:

• The AMP PD platform provides a valuable, harmonized dataset for Parkinson's disease research.
• This initiative aims to facilitate data accessibility and analytical capabilities for researchers globally.
• The findings highlight genetic correlations and risk factors within specific ancestral populations relevant to PD.