|
| 1 | +# Insights Into Parkinson's Disease Genetics in African Populations |
| 2 | + |
| 3 | +## Expanded GWAS Identifies Ancestry-Specific and Cross-Population Risk Loci |
| 4 | + |
| 5 | +`GP2 ❤️ Open Science 😍` |
| 6 | + |
| 7 | +[](https://opensource.org/licenses/MIT) |
| 8 | + |
| 9 | +[](https://zenodo.org/badge/latestdoi/635483971) |
| 10 | + |
| 11 | +**Last Updated:** March 2026 |
| 12 | + |
| 13 | +------------------------------------------------------------------------ |
| 14 | + |
| 15 | +## Overview |
| 16 | + |
| 17 | +This repository accompanies the manuscript: **"Insights Into Parkinson's Disease Genetics in African Populations: Expanded GWAS Identifies Ancestry-Specific and Cross-Population Risk Loci"** |
| 18 | + |
| 19 | +This study represents the argest genome-wide association study (GWAS) |
| 20 | +of Parkinson's disease (PD) in African (AFR) and African-admixed (AAC) |
| 21 | +populations to date. We integrated individual-level genotype data from the Global |
| 22 | +Parkinson's Genetics Program (GP2; release 11) with summary statistics from |
| 23 | +23andMe and the Million Veterans Program (MVP) to better |
| 24 | +characterize the genetic architecture of PD in underrepresented |
| 25 | +populations. |
| 26 | + |
| 27 | +### Summary |
| 28 | +* 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 |
| 29 | +* Key findings confirm and extend known risk loci: |
| 30 | + * GBA1 (rs3115534) was the top signal across all analyses |
| 31 | + * SNCA and SCARB2 replicated as trans-ancestry loci |
| 32 | + * a novel LRRK2 coding variant (p.T1410M) reached genome-wide significance in AFR populations for the first time, alongside two additional novel loci. |
| 33 | + |
| 34 | +### Citation |
| 35 | +If you use this repository or find it helpful for your research, please cite the corresponding manuscript: |
| 36 | +> **Insights Into Parkinson's Disease Genetics in African Populations: Expanded GWAS Identifies Ancestry-Specific and Cross-Population Risk Loci** |
| 37 | +> |
| 38 | +> by Okubadejo et al., Global Parkinson's Genetics Program (GP2) |
| 39 | +> |
| 40 | +> medRxiv 2026; DOI: xx |
| 41 | +
|
| 42 | +------------------------------------------------------------------------ |
| 43 | + |
| 44 | +## Important Note About the 2023 Paper |
| 45 | + |
| 46 | +If you are looking for the original analyses corresponding to: |
| 47 | + |
| 48 | +> *Rizig et al., 2023: "Genome-wide Association Identifies Novel Etiological Insights Associated with Parkinson's Disease in African and African Admixed Populations"* |
| 49 | +
|
| 50 | +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. |
| 51 | + |
| 52 | + |
| 53 | +## Data Statement |
| 54 | +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/. |
| 55 | + |
| 56 | +## Helpful Links |
| 57 | + |
| 58 | +- GP2 Website: https://gp2.org/ |
| 59 | +- GP2 Cohort Dashboard: https://gp2.org/cohort-dashboard-advanced/ |
| 60 | +- GP2 Introduction Paper: |
| 61 | + https://movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mds.28494 |
| 62 | +- GP2 Publications: |
| 63 | + https://pubmed.ncbi.nlm.nih.gov/?term=%22global+parkinson%27s+genetics+program%22 |
| 64 | + |
| 65 | +------------------------------------------------------------------------ |
| 66 | + |
| 67 | +## Workflow Overview |
| 68 | + |
| 69 | + |
| 71 | + |
| 72 | + |
| 73 | +------------------------------------------------------------------------ |
| 74 | + |
| 75 | +## Repository Structure |
| 76 | +``` |
| 77 | +. |
| 78 | +├── analyses |
| 79 | +│ ├── 00_Prepping_Data.ipynb |
| 80 | +│ ├── 01_Covariates.ipynb |
| 81 | +│ ├── 02_GWAS_GP2.ipynb |
| 82 | +│ ├── 03_Munge_Sumstats.ipynb |
| 83 | +│ ├── 04_Meta_Analysis.ipynb |
| 84 | +│ ├── 05_Manhattans_QQs.ipynb |
| 85 | +│ ├── 06_Calculate_Lambdas.ipynb |
| 86 | +│ ├── 07_AA_AFR_Blood.ipynb |
| 87 | +│ └── 08_Forest_Plots.ipynb |
| 88 | +├── figures |
| 89 | +│ └── workflow.png |
| 90 | +├── LICENSE |
| 91 | +├── README.md |
| 92 | +└── tables |
| 93 | +``` |
| 94 | + |
| 95 | +------------------------------------------------------------------------ |
| 96 | + |
| 97 | +## Analysis Notebooks |
| 98 | + |
| 99 | +Languages: Python, R, and Bash |
| 100 | + |
| 101 | +| Notebook | Description | |
| 102 | +| -------------------- | ------------------------------------------------------- | |
| 103 | +| 00_Prepping_Data | Harmonization, phenotype cleaning, and sample filtering | |
| 104 | +| 01_Covariates | Making of covariate file (sex and PCs) | |
| 105 | +| 02_GWAS_GP2 | Cohort-level GWAS in GP2 | |
| 106 | +| 03_Munge_Sumstats | Formatting and QC of summary statistics | |
| 107 | +| 04_Meta_Analysis | AFR, AAC, and combined meta-analyses | |
| 108 | +| 05_Manhattans_QQs | Manhattan and QQ plots | |
| 109 | +| 06_Calculate_Lambdas | Genomic inflation and QC metrics | |
| 110 | +| 07_AA_AFR_Blood | Blood-specific follow-up analyses | |
| 111 | +| 08_Forest_Plots | Cross-cohort forest plots | |
| 112 | + |
| 113 | + |
| 114 | +## Software |
| 115 | + |
| 116 | +| Software | Version(s) | URL | RRID | Notes | |
| 117 | +| --------------------- | ---------- | ---------------------------------------------------------------------------------------------- | ---------- | ------------------------- | |
| 118 | +| ANNOVAR | 2020-06-08 | [http://www.openbioinformatics.org/annovar/](http://www.openbioinformatics.org/annovar/) | SCR_012821 | Variant annotation | |
| 119 | +| METAL | 2020-05-05 | [http://csg.sph.umich.edu/abecasis/Metal/](http://csg.sph.umich.edu/abecasis/Metal/) | SCR_002013 | Meta-analysis | |
| 120 | +| PLINK | 1.9, 2.0 | [http://www.nitrc.org/projects/plink](http://www.nitrc.org/projects/plink) | SCR_001757 | Genetic analyses | |
| 121 | +| Python | 3.9+ | [http://www.python.org](http://www.python.org) | SCR_008394 | pandas, numpy, matplotlib | |
| 122 | +| R | 4.2+ | [http://www.r-project.org](http://www.r-project.org) | SCR_001905 | tidyverse, data.table | |
| 123 | + |
| 124 | + |
| 125 | + |
| 126 | +------------------------------------------------------------------------ |
| 127 | + |
| 128 | +## Acknowledgments |
| 129 | + |
| 130 | +This work was performed on behalf of the Global Parkinson's Genetics |
| 131 | +Program (GP2). We thank all study participants, clinicians, and contributing cohorts |
| 132 | +worldwide. |
0 commit comments