Identify single-cell variance eQTL in the OneK1K cohort

This repository contains the analysis code pipeline to identify single-cell variance eQTL (sc-veQTL) as part of the manuscript "Genetic variants associated with cell-type-specific intra-individual gene expression variability reveal new mechanisms of genome regulation"

In this study, we identified a novel genetic regulation mechanism, where genetic variants affect the variance and dispersion of the intra-individual gene expression independent from mean effects. This list of genes (dGene, i.e., gene with dispersion-eQTL) is enriched in the immune response and interspecies interaction and their cellular dispersion levels are associated with auto-immune disease risk.

Scripts are listed by the order in the methods section of the manuscript:

1. The collection and QC of the OneK1K cohort
2. Generate intra-individual mean, variance, and dispersion matrix for the gene expression
3. The sc- eQTL/veQTL/deQTL association
4. Simulation to evaluate the accuracy of dispersion estimation
5. Pseudotime inference
6. The G x G and G x E interaction test
7. Tras- eQTL and veQTL mapping
8. Replication analysis in non-EUR (East Asian) cohort

The repository will be updated soon after peer review.

Data Availability

The following datasets can be downloaded from Zenodo.

1. Updated OneK1K Seurat object which contains both raw and SCTransformed counts (980 donors and 14 cell types)
2. Imputed and QCed genotype in PLINK format
3. Covariates for QTL analysis (sex, age, genotype PCs, and expression PEER factors)
4. Donor x gene matrix for pseudobulk mean, variance, and dispersion
5. Summary statistics for eQTL, veQTL, and deQTL (both raw and top SNP only)

To request additional datasets, please email Angli Xue (a.xue@garvan.org.au).

Citation

Angli Xue, Seyhan Yazar, José Alquicira-Hernández, Anna S E Cuomo, Anne Senabouth, Gracie Gordon, Pooja Kathail, Chun Jimmie Ye, Alex W. Hewitt, Joseph E. Powell. Genetic variants associated with cell-type-specific intra-individual gene expression variability reveal new mechanisms of genome regulation. Under Review. 2024. (Preprint)

For questions, please email us at Angli Xue (a.xue@garvan.org.au) or Joseph E. Powell (j.powell@garvan.org.au)