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Exploring the Global Landscape of Rare Causal and Common High-Risk Variants in Parkinson’s Disease

GP2 ❤️ Open Science 😍

DOI License: MIT

Last Updated: June 2025

Summary

This repository contains the code and workflow used in the study: “Exploring the Global Landscape of Rare Causal and Common High-Risk Variants in Parkinson’s Disease”.

In this analysis, we screened sequencing (GP2 Release 8) and genotyping (GP2 Release 9) data from 69,881 individuals, including 41,139 clinically affected individuals (PD and other neurodegenerative phenotypes) and 28,742 unaffected individuals (controls, population cohorts, and healthy family members).

The notebooks provided here demonstrate how we extracted variant carriers and metadata, performed initial annotation across multiple ancestries using plink, bcftools, and annovar.

Data Statement

  • The data was obtained from the Global Parkinson’s Genetics Program (GP2) release 8 (GP2 release 8, DOI: 10.5281/zenodo.13755496; GP2 release 9, DOI: 10.5281/zenodo.14510099) and access can be requested through the Accelerating Medicines Partnership in Parkinson’s Disease (AMP-PD) via the online application process (https://www.amp-pd.org/).

Citation

If you use this repository or find it helpful for your research, please cite the corresponding manuscript:

Exploring the Global Landscape of Rare Causal and Common High-Risk Variants in Parkinson’s Disease Lange LM, Fang ZH, Makarious MB, Kuznetsov N, et al., Global Parkinson’s Genetics Program (GP2), 2025 [DOI: pending publication]

Figures and Supplementary Figures

(pending publication)

Tables and Supplementary Tables

(pending publication)

Helpful Links

Repository Orientation

The analyses/ directory includes all the analyses discussed in the manuscript or links to the respective GitHubs where analyses were followed.

THIS REPO
├── LICENSE
├── README.md
├── analyses/
|   ├── 00_GP2_metadata.ipynb
|   ├── 01_GP2_WGS_R8_variant_extraction_and_annotation.ipynb
│   └── 02_GP2_NBA_R9_variant_extraction_and_annotation.ipynb
├── figures/
└── tables/

Analyses

  • Languages: Python, bash
Notebook Description
00_GP2_metadata.ipynb Extract metadata for identified carriers (from GP2 NBA, CES and WGS)
01_GP2_WGS_R8_variant_extraction_and_annotation.ipynb Extract variant carriers and perform annotation using GP2 WGS and CES data (PLINK files from Release 8)
02_GP2_NBA_R9_variant_extraction_and_annotation.ipynb Extract variant carriers and perform annotation using GP2 NBA data (PLINK files from Release 9)

Software

Software Version(s) Resource URL RRID Notes
Python 3.8+ http://www.python.org/ RRID:SCR_008394 Used for downstream analysis and scripting.
PLINK 1.9 / 2.0 http://www.cog-genomics.org/plink/ RRID:SCR_001757 Used for variant filtering and extraction.
BCFtools 1.17+ http://www.htslib.org/ RRID:SCR_005227 Used for variant extraction.
ANNOVAR Latest https://annovar.openbioinformatics.org/en/latest/ RRID:SCR_012821 Used for variant annotation.

Disclaimer

This notebook accompanies the manuscript "Exploring the Global Landscape of Rare Causal and Common High-Risk Variants in Parkinson’s Disease" and is intended to facilitate transparency and reproducibility of the variant extraction and annotation workflow.

About

This is the online repository for the manuscript titled "Exploring the Global Landscape of Rare Causal and Common High-Risk Variants in Parkinson’s Disease".

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