Key words: systems genetics, cardiovascular disease, nutrigenomics
Chronic diseases such as obesity, diabetes and atherosclerosis have both genetic and environmental risk factors, but understanding the complex interactions between susceptibility genes and the environment has been difficult. I am particularly interested in using integrative genetic studies, also called systems genetics, to elucidate the genetic component of these chronic metabolic diseases. The goal of this work is to identify individual genes and/or the interaction of groups of genes, also called biologic networks, contributing to chronic disease.
I currently have 2 projects examining novel aspects of atherosclerosis susceptibility. These loci and metabolites were identified using integrative genetic approaches:
Project 1: Validation of genetic networks conferring atherosclerosis susceptibility. Rationale: Weighted Gene Co-expression Analysis (WGCNA) provides an unbiased analysis of gene expression data by creating groups of genes, called modules that can be related to clinical traits.
Project 2: Identifying and confirming novel metabolites predicting atherosclerotic risk Rationale: Identification and integration of plasma metabolites in our genetic studies can identify biomarkers of atherosclerosis and potential mechanisms by which novel genes affect lesion size and composition.
Diet is also an important risk factor for chronic disease. A long-term goal of my lab is to understand the interactions between diet and genetics polymorphisms that leads to increased disease risk. An integrative systems approach enables us to evaluate how these, diet and genetics, interact across multiple scales of data (transcriptional, proteomic, metabolomics or even meta-genomic) to affect susceptibility. One expanding technology that provides a possible insight between diet and genetic risk are studies quantifying metabolites. Metabolites are potentially biomarkers of disease and provide mechanistic insight into genes and pathways contribute to disease.
Project 3: Systems approaches to gene/diet interactions
Rationale: Systematic perturbation of diet across a genetic population can identify loci and dietary nutrients affecting atherosclerosis.
- Jodi Albright, Technician