Rare variant association testing to mitochondrial copy number in UK Biobank
Author: Vamsee Pillalamarri
This repo contains code (pipeline, scripts, and analysis notebooks) relating to Pillalamarri et al. 2023 HGG Advances "Whole-exome sequencing in 415,422 individuals identifies rare variants associated with mitochondrial DNA copy number" (PMID 36311265, doi: 10.1016/j.xhgg.2022.100147).
This repository is a snapshot of a private repository (ArkingLab/mito_rare-variant
) with more comprehensive access to a variety of resources for the project along with results from the single- and rare-variant burden testing. Please reach out to [email protected]
or [email protected]
for raw BOLT-LMM results from single- and GENESIS aggregate rare-variant burden testing results.
Install BIOCONDUCTOR Install Manager:
if (!require("BiocManager", quietly = TRUE))
install.packages("BiocManager")
Install Bioconductor packages:
BiocManager::install("SeqArray")
BiocManager::install("GENESIS")
-
Aggregate Association Testing using GENESIS: Example call:
Rscript src/scripts/aggregate_association_testing.R 1 --AF.max 0.01 --test SMMAT --qv nonsyn.impact_mod_high --ncores 4
-
Leave one out testing: Example call:
Rscript src/scripts/leave_one_out.R --gene GENE_NAME --chr CHROMOSOME --af_max 0.01 --output results.rds --plot --plot_type SMMAT --save_dir ./plots --cores 4
-
Power analysis:
src/scripts/power-analysis.R
src/scripts/power-analysis.py
(Rewritten in Python)
-
Gene-level conditional variant breakdown functions:
conditional_variants.breakdown.R
-
Single-variant testing using BOLT-LMM:
src/scripts/pipeline_shell_scripts/run.bolt_lmm_adjusted_forGWASsnps.sh
Run as:
# On UKB RAP CLI:
# <log into UKB RAP using `dx login`>
# qrsh -now y -pe local 16 -l h_vmem=5G,mem_free=5G,h_fsize=10G
# OPTIONAL:
# cd /dcs01/arking/arkinglab/software/src/BOLT-LMM/
# module load singularity/3.2
# module load python/
# singularity shell -B /tmp,/dcl01,/dcs01 singularity-bolt-lmm.simg
- Table 1A:
src/analysis_notebooks/Table_1A.Rmd
- Table 1B
src/analysis_notebooks/Table_1B.Rmd
- PheWAS Analyses
src/analysis_notebooks/phewas-analyses.Rmd
- PheWAS Additional Analyses
src/analysis_notebooks/phewas-additional-analyses.Rmd
- Model Genetic Architecture
src/analysis_notebooks/model-genetic-architecture.Rmd
- pVCFs:
/dcl01/arking/data/static/UKBiobank/WES/pVCF
- plink:
/dcl01/arking/data/static/UKBiobank/WES/plink
NOTE: pVCFs combine multiallelic sites into one record, while plink splits them; the plink .bim file reflects this difference
Gene lists can be found in the "resources" folder in this repo, or on JHPCE at /dcl01/arking/data/static/UKBiobank/gene_lists
.
gwas_genes.txt
: Genes identified from GWAS for mtDNA-CNdepletion_genes.txt
: 15 genes known to be causal for mtDNA depletion syndromes
Mitocarta gene pathways: /dcs01/arking/arkinglab/resources/mitoCarta/Human.MitoPathways3.0.gmx