Abstract

Gene expression is an important cellular phenotype under both genetic and environmental control. Changes in gene expression appear to underlie the majority of genetic associations identified in genome-wide association studies of common disease. Studying the genetic regulation of gene expression has thus been a fruitful strategy to unravelling the underlying molecular mechanisms of common disease associated variants. We have collected deep ‘omic level data in the MuTHER study encompassing ~800 deeply-phenotyped twins from the TwinsUK cohort, including transcriptomics in three primary tissues (adipose, skin, whole blood) and one cell line (transformed lymphocytes). Using this dataset we have identified and characterized regulatory variants (eQTLs) across the genome, including a Type 2 Diabetes associated adipose-specific trans-regulatory network which I will discuss. Most common diseases result from both environmental and genetic factors, which can independently influence disease, but may also interact in complex ways. We are thus in parallel exploring the relationship between gene expression and multiple environments (lifestyle factors and biomedical measurements) with the end goal of identifying gene by environment interactions in the regulation of gene expression.