X-Chromosome Wide Association Study of Parkinson's Disease in the South African Population

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Last updated: June 2025

Summary

This repository contains the code, data workflows, and results associated with the manuscript titled "X-Chromosome Wide Association Study of Parkinson's Disease in the South African Population".

This study is an X chromosome wide association (XWAS) analysis for Parkinson’s disease in the South African Study Collection using NeuroBooster array data.

Data statement

Data used in the preparation of this article were obtained from the Global Parkinson’s Genetics Program (GP2; https://gp2.org) release 7 (GP2 release 7, DOI: 10.5281/zenodo.10962119) 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/).

All GP2 data are hosted in collaboration with the Accelerating Medicines Partnership in Parkinson’s disease, and are available via application on the website (https://amp-pd.org/register-for-amp-pd). For up-to-date information on GP2 data acquisition, access, and policies, visit https://gp2.org/. Tier 1 data can be accessed by completing a form on the Accelerating Medicines Partnership in Parkinson’s Disease (AMP®-PD) website (https://amp-pd.org/register-for-amp-pd). Tier 2 data access requires approval and a Data Use Agreement signed by your institution.

Helpful Links

• GP2 Website
  • GP2 Cohort Dashboard
• Introduction to GP2
  • Other GP2 Manuscripts (PubMed)

Citation

(pending publication)

Key analyses:

1. Quality control, file preparation for imputation, and association analysis.
   a. Autosomal quality control pipeline used: https://github.com/MataLabCCF/GWASQC
   b. X chromosome quality control pipeline used: https://github.com/MataLabCCF/XWAS
   c. XWAS pipeline used: https://github.com/MataLabCCF/XWAS_v2
2. P-value significance threshold calculations for both sexes.
3. Plotting of XWAS results.
4. Checking for replication using previously published XWAS for neurodegenerative diseases.

Repository Orientation

• The analysis/ directory includes all analyses discussed in the manuscript.

 THIS_REPO/ 
  ├── analyses/ 
  |     ├── 00_XWAS.sh
  |     ├── 01_NEEF_F.py
  |     ├── 02_NEEF_M.py
  |     ├── 03_plot_PCA_all_target.py
  |     ├── 04_plot_PCA_sexes.py
  |     └── 05_XWAS_replication.sh
  ├── LICENSE
  └── README.md 

Analysis Notebooks

Languages: Python, bash, and R

Directory	Notebooks	Description
analyses/	01_XWAS.sh	This script covers the quality control and file preparation for imputation, association analysis, and p-value calculation file preparation. This also includes post XWAS file preparation for Fuma submission as well as plotting.
analyses/	02_NEEF_F.py	This script covers the p-value significance threshold calculation for the X chromosome in females.
analyses/	03_NEEF_M.py	This script covers the p-value significance threshold calculation for the X chromosome in males.
analyses/	04_plot_PCA_all_target.py	This script plots the PCA for the whole dataset and the reference file (PC1 vs PC2 and PC3 vs PC4).
analyses/	05_plot_PCA_sexes.py	This script plots the PCAs by sex against the reference file (PC1 vs PC2 and PC3 vs PC4).
analyses/	06_XWAS_replication.sh	This script looks for replication in previous XWAS.

Software

Software	Version(s)	Resource URL	RRID	Notes
Python Programming Language	3.7	http://www.python.org/	RRID:SCR_008394	Used throughout the analysis.
PLINK	1.9 and 2.0	http://www.nitrc.org/projects/plink	RRID:SCR_001757	Used for quality control, file preparation, association analysis, and p-value threshold calculation.
R Project for Statistical Computing	v.4.2.0	http://www.r-project.org/	RRID:SCR_001905	Used for plotting.
GWAMA	2.2.2	http://www.geenivaramu.ee/en/tools/gwama	RRID:SCR_006624	Used for meta-analysis of sex-stratified XWAS results.
gcta	1.94.1	https://yanglab.westlake.edu.cn/software/gcta/#Overview	Not available	Used for the association analysis.