Figure 1.

Development of Complex Disease Genetic Studies. First Generation Genetic Studies attempt to relate genetic variants, such as SNPs, directly to a complex disease; these approaches have low power to detect associations and even lower power to detect gene-gene and gene-environment interactions. Second Generation Genetic Studies assess for associations between genetic variants and a single type of –omics data, such as transcriptomics, metabolomics, or proteomics. These studies have provided useful insights into the genetic determinants of these biological intermediate phenotypes, but relating these findings to disease susceptibility has been more difficult. Third Generation Genetic Studies, which will require new methodological development, will explore the relationships between genetic variants and multiple types of -omics data in a network context, potentially with models that address the phenotypic and genetic heterogeneity of complex diseases.