In partial fulfillment of the requirements for the degree of

Master of Science in Biology

in the

School of Biological Sciences

Jared Collins

Will defend his thesis

Mechanisms of Coherence and Incoherence Between Single-Cell eQTL and GWAS Effects in Crohn’s Disease

17th April 2023

10 AM

Kandeda Building Seminar Room 118

https://gatech.zoom.us/j/91528278340?pwd=b1hTVE83V2ljQlU2NEtZR0FBQ1VDZz09

Thesis Advisor:

Dr. Greg Gibson

School of Biological Sciences

Georgia Institute of Technology

Committee Members:

Dr. Joseph Lachance

School of Biological Sciences

Georgia Institute of Technology

Dr. Jingjing Yang

School of Medicine

Emory University

Abstract:

               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.