One aspect of common complex disease is that the development of disease and disease phenotypes quite often present along a broad spectrum of symptoms and share clinical characteristics, endo-phenotypes, or quantitative traits with closely related disorders [25] . This is evident in gene sharing, as mentioned above, and equally in the overlap of biological pathways between related disorders. Using GAD disease gene sets, Venn diagram comparisons among related disorders shows modest gene sharing. However, when gene sets are then placed into biological pathways and compared by Venn analysis, there is a marked increase in the overlap in pathways between related disorders. This was not found in gene sets from unrelated disorders. For example, major autoimmune disorders quite often share endophenotypes of lymphoproliferation, autoantibody production, and alterations in apoptosis, as well as other immune cellular and biochemical aberrations. As shown in Figure 1a , genes that have been positively associated with type 1 diabetes, rheumatoid arthritis, and Crohn's disease show a modest overlap. However, when individual gene sets are fitted into biological pathways, then compared for overlap of pathway membership, there is a striking increase in the overlap at the pathway level. This is true in a comparison of gene and pathways for type 2 diabetes, insulin resistance, and obesity as well (Figure 1b ). This pattern of major pathway overlap does not seem to occur between unrelated disorders, such as insulin resistance, rheumatoid arthritis and bipolar disorder (Figure 1c ). This disease related sharing at the pathway level suggests common regulatory mechanisms between these disorders and that the original positive associations are not necessarily due to random chance alone.