The LRRK2 p.A419V risk variant influences age of onset for Parkinson's disease in East Asian populations

GP2 ❤️ Open Science 😍

Summary

This is the online repository for the manuscript titled "The LRRK2 p.A419V risk variant influences age of onset for Parkinson's disease in East Asian populations". This study aims to resolve inconsistencies in previous reports by providing robust evidence that that the LRRK2 p.A419V is a significant risk player for PD in the EAS population while looking into data from multiple ancestries. The study also explores the variant's association with age at onset.

Data Statement

• All GP2 data are hosted in collaboration with the Accelerating Medicines Partnership in Parkinson's Disease and are available via application on the website. The GP2 PD case and control data are available via the GP2 website (https://gp2.org; release 9: https://doi.org/10.5281/zenodo.10472143). Genotyping imputation, quality control, ancestry prediction, and processing were performed using GenoTools (v1.0.0), publicly available on GitHub
• UKB statement?
• The All of Us genomic data are available under restricted access for human subject data. Access can be obtained by following the instructions under the All of Us workbench
• For EAS-WES data, Individual-level genotype data will be made available upon reasonable request and after approval by the relevant institutional review board. Please refer to Data availability section in Chew, E.G., Liu, Z., Li, Z. et al. Nat Aging. 2025 (https://doi.org/10.1038/s43587-024-00760-7) for more information.

Repository Orientation

THIS_REPO
└── README.md
└── analysis
    └── AMP-PD
    |   └── 01_A419V_AMP-PD.ipynb    
    ├── GP2
    |   ├── 00_A419V_data_preparation.ipynb
    |   ├── 01_A419V_variant_analysis_release9.ipynb
    |   ├── 02_A419V_haplotype_release9.ipynb
    |   └── 03_A419V_AAO_analysis_release9.ipynb
    └── AllOfUs

Notebooks Description

• Languages: Python, bash, and R

Directory	Notebook	Description
GP2/	00_A419V_data_preparation.ipynb	Downloading and structuring data
	01_A419V_variant_analysis_release9.ipynb	Analyzes GP2 genotyped data across ancestries
	02_A419V_haplotype_release9.ipynb	Analyzes haplotype around A419V in GP2 genotyped data
	03_A419V_AAO_analysis_release9.ipynb	Analyzes Age of Onset for PD A419V carrier and non-carrier
AMP-PD/	01_A419V_AMP-PD.ipynb	Analyzes AMP-PD whole-genome sequencing data
AllOfUs/	01_LRRK2_A419V_AllofUs.ipynb	Analyzes All-of-us whole-genome sequencing data

Software

Software	Version(s)	Resource URL	RRID	Notes
Python Programming Language	3.10	http://www.python.org/	RRID:SCR_008394	pandas; numpy; seaborn; matplotlib; statsmodel; rpy2; used for general data wrangling/plotting/analyses
R Project for Statistical Computing	4.4.2	http://www.r-project.org/	RRID:SCR_001905	tidyverse; dplyr; tidyr; ggplot2; car; cowplot; grid; RColorBrewer; forestmodel; survival; used for general data wrangling/plotting/analyses
PLINK	1.9 and 2.0	http://www.nitrc.org/projects/plink	RRID:SCR_001757	used for genetic analyses