GP2 ❤️ Open Science 😍
Last updated: July 2026
This is the online repository for the manuscript titled "Multi-ancestry rare variant burden analysis of E3 ubiquitin ligase genes in Parkinson’s disease". This repository contains the code used to perform a multi-ancestry rare variant burden analysis of seven E3 ubiquitin ligase genes (HERC1, IRF2BPL, KMT2D, RAPSN, RNF168, RNF216, and TRIM2) in Parkinson's disease using GP2 Release 11 whole-genome sequencing data. The analysis includes variant filtering, annotation, burden testing with SKAT-O, and multiple-testing correction to evaluate the contribution of rare variants to Parkinson's disease risk, including early-onset Parkinson's disease (EOPD). Although no statistically significant associations were identified after multiple-testing correction, this repository provides a reproducible workflow for rare variant association analyses in large multi-ancestry genomic datasets.
Data used in the preparation of this article were obtained from the Global Parkinson’s Genetics Program (GP2; https://gp2.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.
In this analysis we used Tier 2 GP2 Release 11 data (10.5281/zenodo.17753486)
- The
analysis/directory includes all analyses discussed in the manuscript.
THIS_REPO/ ├── analyses/ | ├── WGS_E3_PD_burden.ipynb | └── WGS_E3_EOPD_burden.ipynb ├── figures/ | ├── Supplementary_Figure_S1.pdf | ├── Supplementary_Figure_S2.pdf | ├── Supplementary_Figure_S3.pdf | ├── Supplementary_Figure_S4.pdf | └── Supplementary_Figure_S5.pdf ├── tables/ | ├── Supplementary_Data_1.csv | ├── Supplementary_Data_2.csv | ├── Supplementary_Data_3.csv | └── Supplementary_Data_4.csv ├── LICENSE └── README.md
| Directory | Notebooks | Description |
|---|---|---|
analyses/ |
WGS_E3_PD_burden.ipynb |
Rare variant burden analysis in the Parkinson's disease (PD) cohort. |
analyses/ |
WGS_E3_EOPD_burden.ipynb |
Rare variant burden analysis in the early-onset Parkinson's disease (EOPD) cohort. |
|
| Software | Version(s) | Resource URL | RRID | Notes |
|---|---|---|---|---|
| ANNOVAR | d.06.08.2020 | http://www.openbioinformatics.org/annovar/ | RRID:SCR_012821 | Used for variant annotation. |
| PLINK | v.1.9,v. 2.0 | http://www.nitrc.org/projects/plink | RRID:SCR_001757 | Used for genetic analyses. |
| Python Programming Language | 3.7, 3.8, 3.9, 3.10 | http://www.python.org/ | RRID:SCR_008394 | pandas; numpy; seaborn; matplotlib; statsmodel; Used for general data wrangling/plotting/analyses |
| RVTests | v.2.1.0 | http://genome.sph.umich.edu/wiki/RvTests | RRID:SCR_007639 | Used for burden analyses. |
- Supplemendtary Data 1. Single-variant association analysis results in the PD cohort.
- Supplementary Data 2. Single-variant association analysis results in the EOPD cohort.
- Supplementary Data 3. Gene-based burden analysis results in the PD cohort (SKAT-O).
- Supplementary Data 4. Gene-based burden analysis results in the EOPD cohort (SKAT-O).
- Supplementary Figure S1. Overlap of potentially functional rare variants across ancestry groups in the PD cohort.
- Supplementary Figure S2. Overlap of coding variants across ancestry groups in the PD cohort.
- Subpplementary Figure S3. Overlap of variants with CADD > 20 across ancestry groups in the PD cohort.
- Supplementary Figure S4. Overlap of loss-of-function (LoF)* variants across ancestry groups in the PD cohort.
- Supplementary Figure S5. Overlap of potentially functional, coding, high CADD (>20), and loss-of-function (LoF) rare variants across ancestry groups in the EOPD cohort.