TMEM175, SCARB2 and CTSB associations with Parkinson's disease risk across populations

GP2 ❤️ Open Science 😍

Last Updated: November 2025

Summary

This is the online repository for the manuscript titled "TMEM175, SCARB2 and CTSB associations with Parkinson's disease risk across populations". This study focuses on exploring the role of lysosomal related genes(TMEM175, SCARB2, CTSB and GBA1) in existing PD/control datasets from GP2 Neurobooster genotyping array.

Data statement

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/.

All data was using GP2 release 10 (10.5281/zenodo.15748014). Genotyping imputation, quality control, ancestry prediction, and processing were performed using GenoTools (v1.0.0), publicly available on GitHub.

Helpful Links

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

Citation

(pending publication)

Repository Orientation

• The analyses/ directory includes all analyses discussed in the manuscript.
• The GP2/ directory includes 3 notebooks on processing and analyzing GP2 Neuobooster array data from release 10.

 THIS_REPO/ 
  ├── LICENSE
  ├── README.md 
  └── analyses/ 
       └── GP2/ 
           ├── 00_TMEM175_ALL_GLM.ipynb 
           ├── 01_SCARB2_ALL_GLM.ipynb 
           ├── 02_CTSB_ALL_GLM.ipynb
           ├── 03_GBA1_exclusion_and_scree_plot.ipynb
           ├── 04_forest_plot_and_multiple_test.ipynb
           └── 05_coloc.ipynb 

Analysis Notebooks

Languages: Python, bash, and R

Directory	Notebooks	Description
GP2/	00_TMEM175_ALL_GLM.ipynb	Association analysis, GLM analysis, GCTA-COJO analysis, single variant based and gene based analysis of TMEM175 with GP2 Neurobooster array
GP2/	01_SCARB2_ALL_GLM.ipynb	Association analysis, GLM analysis, GCTA-COJO analysis, single variant based and gene based analysis of SCARB2 with GP2 Neurobooster array
GP2/	02_CTSB_ALL_GLM.ipynb	Association analysis, GLM analysis, GCTA-COJO analysis, single variant based and gene based analysis of CTSB with GP2 Neurobooster array
GP2/	03_GBA1_exclusion_and_scree_plot.ipynb	Exclude GBA1 carriers and get a PCA scree plot in EUR ancestry
GP2/	04_forest_plot_and_multiple_test.ipynb	Multiple test correction and plotting
GP2/	05_coloc.ipynb	Colocalization analysis with eQTL public dataset

Software

Software	Version(s)	Resource URL	RRID	Notes
ANNOVAR	2020-06-08	http://www.openbioinformatics.org/annovar/	RRID:SCR_012821	Used for variant annotation.
PLINK	1.9 and 2.0	http://www.cog-genomics.org/plink/	RRID:SCR_001757	Used for association analyses.
GCTA	1.94.1	https://yanglab.westlake.edu.cn/software/gcta/#Overview	-	Used for conditional analysis.
RVTests	2019-02-05	http://zhanxw.github.io/rvtests/	RRID:SCR_007639	Used for burden tests.
LDpair	Latest	https://ldlink.nih.gov/?tab=ldpair	-	Used for estimating linkage disequillibrium.
Python Programming Language	3.10.15	http://www.python.org/	RRID:SCR_008394	pandas; numpy; seaborn; matplotlib; statsmodel; Used for general data wrangling/plotting/analyses
R Project for Statistical Computing	4.3.3	http://www.r-project.org/	RRID:SCR_001905	forestplot (3.1.7), coloc(5.2.3); Used for data wrangling and visualization