Leveraging Expression Quantitative Trait Loci to Elucidate the Genetic Architecture of Type 2 Diabetes

The enrichment of eQTLs mapped in insulin-responsive peripheral tissues among sets of T2D-associated variants suggests an important role for gene regulation in the genetic basis of T2D. In this body of work, I address outstanding questions about the overall contribution of regulatory variation to genetic susceptibility for T2D and the resolution of genes mapped as putative T2D genes. I employ heritability partitioning to determine the contribution of eQTLs mapped in human adipose tissue and skeletal muscle tissue to the proportion of T2D heritability attributable to common genetic variation. I then address the issue of gene mapping by predicting the genetic component of gene expression from eQTL data and sequentially test for association with T2D using a method that explicitly addresses the mechanism of transcription.