Nancy J. Cox, Ph.D.
Director, Vanderbilt Genetics Institute
Director, Division of Genetic Medicine
Mary Phillips Edmonds Gray Professor of Genetics
Vanderbilt University School of Medicine
Integrating genome and transcriptome for discovery across the medical phenome
We have used the PrediXcan approach (Gamazon et al, Nat Genet 2015) to integrate genome variation with transcriptome measurement to allow us to “impute” transcript levels for genes in BioVU, the biobank at Vanderbilt University. BioVU today has DNA on > 218,000 subjects and electronic health records (EHR) going back more than 20 years in some subjects and > 10 years on average. Applying PrediXcan to BioVU data allows us to create a gene x medical phenome catalog; it is the equivalent of knocking down the expression of each gene in the genome and using as the read-out of the consequences of the knock-down experiment the entire medical phenome, and similarly up regulating the expression of each gene, and reading out the consequences for that experiment over the entire medical phenome. Rather than manipulating the expression of genes, however, we are merely taking advantage of natural variation in the genetically determined expression of each gene to do this experiment. I will describe how we are using this catalog to better understand the relationship be genome variation and the medical phenome, and how using a biobank where we can consider the entire medical phenome rather than one disease at a time can help to inform our understanding of both genetic and disease mechanisms.
