Biobank-scale characterization of Alzheimer’s disease and related dementias identifies potential disease-causing variants, risk factors, and genetic modifiers across diverse ancestries

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Last Updated: November 2024

Summary

This is the online repository for the article titled " Biobank-scale characterization of Alzheimer’s disease and related dementias identifies potential disease-causing variants, risk factors, and genetic modifiers across diverse ancestries". This study aims to conduct genetic characterization of key genes associated with dementia across different ancestry populations using the largest biobank-scale datasets, including All of Us, UK Biobank, ADSP, AMP-PD, and 100KGP. We also assessed 21 previously reported protective and resilient variants among all APOE carriers across all ancestries and datasets.

Pre-print link: pending

Data Statement

• The All of Us genomic data are available under restricted access for human subject data. Access can be obtained by following the instructions under the AllofUs workbench

• Primary data from the 100KGP, which are held in a secure Research Environment, are available to registered users. Please see https://www.genomicsengland.co.uk/about-gecip/for-gecip-members/data-and-data-access for further information

  Repository Orientation

• The analyses/ directory includes all analyses discussed in the manuscript

THIS_REPO
├── README.md
└── analyses
    ├── 00_ADSP.ipynb
    ├── 00_AMP_PD.ipynb
    ├── 00_AllofUs.ipynb
    ├── 00_UKB.ipynb
    ├── 01_Visualization.ipynb
    ├── 02_Regression_analysis.ipynb
    └── 03_R2_and_Interaction_models.R

Analysis Notebooks

• Languages: Python, R, and Bash

Notebook	Description
00_UKB	Fetch cohorts, ancestry info, remove related individuals, filter non-WGS, combine pVCFs, normalize VCFs, annotate, allele freqs, APOE genotyping, phenotype data, resilience/protective variants
00_AMP_PD	Check variants, APOE genotyping, define cases/controls by ancestry, demographic data, resilience/protective variants
00_AllofUs	Create cohorts (AD, Dementia, Control), gene characterization, Genotools prep and application, allele freqs, APOE genotyping, ancestry definition, demographic data, resilience/protective variants
00_ADSP	Check variants, allele freqs, calculate missingness, APOE genotyping, demographic data, resilience/protective variants
01_Visualization	visualization, including: heatmaps, barplots for APOE genotypes, mutation sites on protein structures, beta values using Upset plots, and PCA plots
02_Regression_analysis.ipynb	Using logistic regression to analyze the protective and conditional models and create covariate files for r2 and interaction models
03_R2_and_Interaction_models.R	Linear regression models adjusted by APOE status, sex, age, and PCs as well as interaction models between APOE status and specific variants