A TWAS-based investigation of gene expression mediated VTE risk

Abstract

The corpus of GWAS has been successful in identifying many genetic loci associated with a large array of diseases, phenotypes, and other outcomes. However, the underlying molecular mechanisms behind such outcomes remain challenging to elucidate. The mediation of gene expression by genotypic variability is potentially one such molecular mechanism. Here, we utilize complementary TWAS methods and leverage four distinct transcriptomic studies (n = 153 - 1414) along with a recently completed meta-GWAS of VTE risk (n = 187,204) to investigate potential correlations between gene expression and genetic risk of VTE. We have imputed predicted expression into the much larger GWAS dataset and have identified six TWAS significant genes that do not overlap with previous VTE GWAS loci. The work here demonstrates the utility of combining the large sample sizes of summary-level GWAS and the denser, less accessible gene expression datasets.