PhD student in functional genomics – identifying non-coding variants regulating gene expression

We are looking to recruit a computational PhD student in functional genomics to join Emma Davenport’s group at the Wellcome Sanger Institute. This is a BBSRC Collaborative Training Partnerships (CTP) studentship in collaboration with AstraZeneca (AZ) and will include a 3-month placement with the industry partner.

Common chronic diseases have complex, multifactorial aetiologies involving the interplay of both genetic and environmental risk factors. Genome-wide association studies (GWAS) have been helpful in discovering the general genomic regions of susceptibility for complex traits. However, identifying the causal variant within the locus and the mechanism by which it exerts its effect remains a challenge. The identified variants are often not causal, but rather proxies for nearby causal variants, which could be present at rare or intermediate frequencies. Furthermore, the majority of GWAS variants are non-coding, suggesting they may exert their effect through the regulation of gene expression. To make use of non-coding DNA variation in a precision medicine context, we need a better understanding of the causal variants affecting gene expression.

Our group integrates gene expression with genotyping data through expression quantitative trait locus (eQTL) mapping to identify genetic variants regulating gene expression. The student will have access to large cohorts of individuals with RNA-sequencing data available, for example, the INTERVAL cohort (n=5,000), to conduct in-depth analysis on how non-coding variants regulate gene expression in normal human physiology. This information can then be applied to cohorts of disease patients to understand how non-coding variants are contributing to disease. As an initial case study to demonstrate the utility of this approach, we will focus on cohorts of patients with respiratory disease (Sanger) and specifically with asthma (AZ).