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 updated OneK1K Seurat object which contains both raw and SCTransformed counts can be downloaded from this link.

For covariates used in the QTL association analysis, 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)