(Georgia Institute of Technology, 2023-05-02)
Collins, Jared Blake
The integration of expression quantitative trait loci with GWAS data has proven invaluable in the exploration of mechanisms through which genetic variants influence complex traits. However, it has also highlighted instances of incoherence in which the eQTL effects of GWAS risk variants seemingly contradict observed case and control expression. Patterns of incoherence may indicate variants associated with disease via protection, but due to the highly heterogenous nature of varying cell-types, may also indicate cell-type specific associations with disease that are convoluted by bulk RNA sequencing. Here, we conduct exploratory analysis integrating sceQTL and GWAS data associated with Crohn’s Disease to assess patterns of coherence and incoherence, using both bulk RNA-seq and predicted single-cell gene expression for case-control expression. We show that integration of GWAS summary statistics with single-cell eQTL data is a promising approach for uncovering cell type specific patterns of coherence and incoherence, and may suggest functional mechanisms underlying these associations.