Harvard TH Chan School of Public Health, Channing Division of Network Medicine, and Dana-Farber Cancer Institute
One of the central tenants of biology is that our genetics—our genotype—influences the physical characteristics we manifest—our phenotype. But with more than 25,000 human genes and more than 6,000,000 common genetic variants mapped in our genome, finding
associations between our genotype and phenotype is an ongoing challenge. Indeed, genome-wide association studies have found thousands of small effect size genetic variants that are associated with phenotypic traits and disease. The simplest explanation is
that these genetic variants work synergistically to help define phenotype and to regulate processes that are responsible for phenotypic state transitions. We will use gene expression and genetic data to explore gene regulatory networks, to study phenotypic
state transitions, and to analyze the connections between genotype, gene expression, and phenotyope. We have found that the networks, and their structure, provide unique insight into how genetic elements interact with each other and the structure of the network
has predictive power for identifying SNPs likely to be associated with phenotype through genome wide association studies. I will show multiple examples, drawing on my work in cancer, in chronic obstructive pulmonary disease, and in the analysis of data from
thirty-eight tissues provided by the Genotype-Tissue Expression (GTEx) project. In particular, we will examine how network features can serve as biomarkers, providing new insights into disease.