Multi-ancestry analysis of POLG variants in Parkinson’s disease

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Last updated: April 2026

Summary

This is the online repository for the manuscript titled "Multi-ancestry analysis of POLG variants in Parkinson’s disease".

The notebooks generated for this manuscript are deposited here in this repository. To investigate the genetic spectrum and prevalence of POLG variants in PD across diverse ancestries, we performed POLG rare variant screening, case-control analysis, segregation analysis and rare burden test.

Based on the findings, POLG variants are overall rare in PD patients but we identified rare pathogenic variants among PD cases, suggesting that POLG-related mitochondrial dysfunction may contribute to PD in isolated instances, particularly under recessive inheritance.

Data statement

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 GP2 Release 11 Tier 2 data (DOI 10.5281/zenodo.17753486)

Helpful Links

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

Repository Orientation

• The analysis/ directory includes all analyses performed for this manuscript.

 POLG_multiancestry/ 
  ├── analysis/ 
  |     ├── 00_POLG_WGS_variant_extraction.ipynb
  |     ├── 01_POLG_CES_variant_extraction.ipynb
  |     ├── 02_POLG_segregation_analysis.ipynb
  |     ├── 03_POLG_burden_analysis.ipynb
  |     └── 04_POLG_case_control_analysis.ipynb
  ├── LICENSE
  └── README.md 

Analysis Notebooks

Languages: Python and bash

Directory	Notebooks	Description
analysis/	00_POLG_WGS_variant_extraction.ipynb	Rare variant extraction of POLG from WGS
analysis/	01_POLG_CES_variant_extraction.ipynb	Rare variant extraction of POLG from CES
analysis/	02_POLG_segregation_analysis.ipynb	Segregation analysis
analysis/	03_POLG_burden_analysis.ipynb	Burden analysis
analysis/	04_POLG_case_control_analysis.ipynb	Case-control analysis

Software

Software	Version(s)	Resource URL	RRID	Notes
ANNOVAR	d.06.08.2020	http://www.openbioinformatics.org/annovar/	RRID:SCR_012821	Used for variant annotation.
BCFtools	v.1.17+	http://samtools.sourceforge.net/mpileup.shtml	RRID:SCR_005227	Used for genomic file manipulation.
GenoTools	v.1.2.3	https://github.com/GP2code/GenoTools	NA	Used for quality control and genetic ancestry inferrence.
gnomAD	v.4.1	http://gnomad.broadinstitute.org/	RRID:SCR_014964	Used to retrieve population frequency data.
PLINK	v.1.9, v.2.0	http://www.nitrc.org/projects/plink	RRID:SCR_001757	Used for genetic analyses.