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Insights Into Parkinson's Disease Genetics in African Populations

Expanded GWAS Identifies Ancestry-Specific and Cross-Population Risk Loci

GP2 ❤️ Open Science 😍

License: MIT

DOI

Last Updated: March 2026


Overview

This repository accompanies the manuscript: "Insights Into Parkinson's Disease Genetics in African Populations: Expanded GWAS Identifies Ancestry-Specific and Cross-Population Risk Loci"

This study represents the argest genome-wide association study (GWAS) of Parkinson's disease (PD) in African (AFR) and African-admixed (AAC) populations to date. We integrated individual-level genotype data from the Global Parkinson's Genetics Program (GP2; release 11) with summary statistics from 23andMe and the Million Veterans Program (MVP) to better characterize the genetic architecture of PD in underrepresented populations.

Summary

  • Integrated GP2, 23andMe, and Million Veterans Program data (3,975 cases, 319,883 controls), conducting separate and combined GWAS in African and African admixed ancestry populations prior to meta-analysis
  • Key findings confirm and extend known risk loci:
    • GBA1 (rs3115534) was the top signal across all analyses
    • SNCA and SCARB2 replicated as trans-ancestry loci
    • a novel LRRK2 coding variant (p.T1410M) reached genome-wide significance in AFR populations for the first time, alongside two additional novel loci.

Citation

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

Insights Into Parkinson's Disease Genetics in African Populations: Expanded GWAS Identifies Ancestry-Specific and Cross-Population Risk Loci

by Okubadejo et al., Global Parkinson's Genetics Program (GP2)

medRxiv 2026; DOI: xx


Important Note About the 2023 Paper

If you are looking for the original analyses corresponding to:

Rizig et al., 2023: "Genome-wide Association Identifies Novel Etiological Insights Associated with Parkinson's Disease in African and African Admixed Populations"

please use the main branch of this repository, found here: https://github.com/GP2code/GP2-AFR-AAC-metaGWAS/tree/main. The current branch contains the expanded 2026 analyses and should be cited for the new manuscript.

Data Statement

Data used in the preparation of this article were obtained from GP2. Specifically, we used Tier 2 data from GP2 (release 11; DOI 10.5281/zenodo.17753486). GP2 data can be accessed through AMP PD (https://amp-pd.org). For the MVP dataset, PD summary statistics from the Million Veteran's Program (MVP) were downloaded from dbGAP (accession number: phs002453.v1.p1; analysis accession: pha010400.1). Summary statistics from 23andMe were shared under a collaborative agreement, submitted at https://research.23andme.com/collaborate/.

Helpful Links


Workflow Overview

Workflow Diagram


Repository Structure

.
├── analyses
│   ├── 00_Prepping_Data.ipynb
│   ├── 01_Covariates.ipynb
│   ├── 02_GWAS_GP2.ipynb
│   ├── 03_Munge_Sumstats.ipynb
│   ├── 04_Meta_Analysis.ipynb
│   ├── 05_Manhattans_QQs.ipynb
│   ├── 06_Calculate_Lambdas.ipynb
│   ├── 07_AA_AFR_Blood.ipynb
│   └── 08_Forest_Plots.ipynb
├── figures
│   └── workflow.png
├── LICENSE
├── README.md
└── tables

Analysis Notebooks

Languages: Python, R, and Bash

Notebook Description
00_Prepping_Data Harmonization, phenotype cleaning, and sample filtering
01_Covariates Making of covariate file (sex and PCs)
02_GWAS_GP2 Cohort-level GWAS in GP2
03_Munge_Sumstats Formatting and QC of summary statistics
04_Meta_Analysis AFR, AAC, and combined meta-analyses
05_Manhattans_QQs Manhattan and QQ plots
06_Calculate_Lambdas Genomic inflation and QC metrics
07_AA_AFR_Blood Blood-specific follow-up analyses
08_Forest_Plots Cross-cohort forest plots

Software

Software Version(s) URL RRID Notes
ANNOVAR 2020-06-08 http://www.openbioinformatics.org/annovar/ SCR_012821 Variant annotation
METAL 2020-05-05 http://csg.sph.umich.edu/abecasis/Metal/ SCR_002013 Meta-analysis
PLINK 1.9, 2.0 http://www.nitrc.org/projects/plink SCR_001757 Genetic analyses
Python 3.9+ http://www.python.org SCR_008394 pandas, numpy, matplotlib
R 4.2+ http://www.r-project.org SCR_001905 tidyverse, data.table

Acknowledgments

This work was performed on behalf of the Global Parkinson's Genetics Program (GP2). We thank all study participants, clinicians, and contributing cohorts worldwide.

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All materials for "Genome-wide Association Identifies Novel Etiological Insights Associated with Parkinson’s Disease in African and African Admixed Populations"

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