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, and to explore how cancer-risk SNPs exert an influence on the disease risk that extends beyond one locus.
1. Genes and genetic variants work together in complex networks that are associated with individual phenotypes and change as phenotype evolves and changes.
2. Differences in network structure can help us to better understand the drivers of health and disease.
3. Networks and their structures can help us understand how small-effect genetic variants can work collectively to influence disease risk.