The Global Parkinson’s Disease Genetics (GP2) Genome Browser

GP2 ❤️ Open Science 😍

Last Updated: December 2025

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Summary

This repository accompanies the brief report “The Global Parkinson’s Disease Genetics (GP2) Genome Browser.”

The GP2 Genome Browser is an open-access platform that provides gene- and variant-level information from one of the largest ancestry-diverse sequencing datasets assembled for Parkinson’s disease (PD) research.

The browser integrates:

• 31,665 whole-genome sequences (WGS)
• 9,559 clinical exomes (CES)
• 11 genetically determined ancestries

using a unified joint-calling, QC, and annotation pipeline (DeepVariant → GLnexus → GenoTools → VEP). It enables:

• Gene-level pages with annotations, resources, and constraint metrics
• Variant-level pages showing functional consequence, allele frequencies, ClinVar, dbSNP, and CADD
• Frequency tables stratified by ancestry and phenotype (Case / Control / Other)

The GP2 Genome Browser is openly available at:
https://gp2.broadinstitute.org

This repository contains the script used to produce the browser-ready Hail tables and frequency outputs used in the manuscript.

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Citation

If you use this repository or find it helpful, please cite:

Fang Z-H., Grant R.H., Vitale D., Hernandez C.F., Hong S., Leonard H.L., Makarious M.B., Lange L.M., Solomonson M., Heutink P., Dilliott A., Ghosh Galvelis K., Nalls M.A., Singleton A.B., Blauwendraat C., and the Global Parkinson’s Genetics Program (GP2).
The Global Parkinson’s Disease Genetics (GP2) Genome Browser (2025).

Manuscript DOI: coming soon
GitHub DOI: DOI 10.5281/zenodo.17903069

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Data Statement

• GP2 WGS Data

  • GP2 Release 10 (WGS): DOI 10.5281/zenodo.15748014
  • Accessible via AMP-PD: https://amp-pd.org

• GP2 CES Data

  • GP2 Release 8 (PDGENEration CES): DOI 10.5281/zenodo.13755496

• Additional Controls

  • Alzheimer’s Disease Sequencing Project (ADSP) WGS: DOI 10.60859/z6z9-9692, accessed via NIAGADS

• Variant Processing Pipeline

  • Single-sample calling: DeepVariant v1.6.1
  • Joint-genotyping: GLnexus v1.4.3
  • Quality control: genotype-, sample-, and variant-level filters from AMP-PD & GP2
  • Genetic ancestry assignment: GenoTools v1.2.3
  • Annotation: Ensembl VEP v111 (adds ClinVar, CADD, dbSNP, functional consequence)
  • Intergenic variants excluded from browser display
  • Allele frequencies computed by genetic ancestry and phenotype

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Helpful Links

• GP2 Website: https://gp2.org
  • GP2 Cohort Dashboard: https://gp2.org/cohort-dashboard-advanced
• AMP-PD: https://amp-pd.org
• PDGENEration: https://www.parkinson.org/PDGENEration
• ADSP / NIAGADS: https://www.niagads.org
• GP2 Overview: https://movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mds.28494
• GP2 Manuscripts:
  https://pubmed.ncbi.nlm.nih.gov/?term=%22global+parkinson%27s+genetics+program%22

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Repository Orientation

├── LICENSE.txt
├── README.md
└── analyses/
    └── gp2_genome_browser_hail_table.ipynb

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Analysis Notebook

Languages: Python (Hail), and bash

Description:
This notebook performs all steps needed to generate the tables consumed by the GP2 Genome Browser, including:

• Importing GP2, AMP-PD, and ADSP Hail tables
• Applying genotype-, sample-, and variant-level QC
• Merging WGS and CES high-quality datasets
• Annotating variants with VEP, ClinVar, dbSNP, and CADD
• Assigning genetic ancestry groups (via precomputed metadata)
• Calculating allele frequencies stratified by ancestry & phenotype
• Exporting browser-ready tables for gene and variant pages

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Software

Software	Version	URL	RRID	Notes
Python	3.9 / 3.10	http://python.org	RRID:SCR_008394	Main analysis environment
R	4.2	http://www.r-project.org	RRID:SCR_001905	Used for summary figures
Hail	0.2.x	https://hail.is	—	Variant processing, QC, tables
DeepVariant	1.6.1	https://github.com/google/deepvariant	—	Single-sample variant calling
GLnexus	1.4.3	https://github.com/dnanexus-rnd/GLnexus	—	Joint-genotyping (DV-WGS / DV-WES presets)
GenoTools	1.2.3	https://github.com/GP2code/GenoTools	—	Genetic ancestry assignment
VEP	v111	https://ensembl.org/info/docs/tools/vep/	RRID:SCR_007931	Variant consequence + annotation
KING	2.3.0	https://kingrelatedness.com	RRID:SCR_009251	Relatedness inference

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Data & Code Availability

• GP2 and AMP-PD datasets are available through application via AMP-PD (https://amp-pd.org).
• ADSP data are available via NIAGADS (NG00067; DOI: 10.60859/z6z9-9692).
• Code in this repository reproduces browser-ready data tables and manuscript figures.
• A permanent Zenodo archive of this repository will be linked via the DOI badge above.

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