Gene expression and copy number variation in common complex diseases

Common, complex diseases are not caused by a single gene mutation but rather have genetic and environmental components. As a subset, autoimmune diseases also possess robust gene expression signatures that have both genetic and environmental contributions. We explored gene expression signatures in type 2 diabetes, coronary artery disease, and their precursor state metabolic syndrome, and identified overlapping gene expression signatures exhibiting greater resemblance to each other than to an autoimmune disease. These signatures are consistent with activation of the innate immune response. Genetic variations contribute to familiality and we sought to determine if large-scale genomic variants, copy number variants (CNVs), are associated with common, complex diseases. To do so, we first developed methods to identify CNVs from SNP-based arrays. We analyzed genomic variation in type 1 diabetes and identified CNVs that were differentially present in patients with or at high risk for type 1 diabetes versus control. Thus, we conclude that both gene expression profiles and genomic variants are easily detected clinical markers that may be useful predictors of disease liability and serve to identify new classes of therapeutic targets.