Type 2 diabetes (T2D) is a complex disease caused by an interaction between genetic susceptibility and environmental factors, chiefly insulin resistance. Most of the genetic contribution to T2D is through b-cell function. Most of the environmental contribution is due to obesity. The epidemic of T2D is caused by the obesity epidemic; an increased demand for insulin causes people with limited b-cell function to develop T2D.
T2D is a polygenic disease where multiple gene loci make small contributions to the overall disease. But, the many genes that can affect T2D susceptibility affect a relatively small number of biological processes. The challenge is to piece together these processes and identify the spots that confer disease vulnerability or can be responsive to therapeutics.
The advent of –omics technologies (e.g. transcriptomics, proteomics, metabolomics) has increased the scope of phenotypes that can be obtained in people with diseases and in model organisms. The challenge is to identify which phenotypes are indeed causal for a disease and to place them in a pathway leading to the disease.
Genetics provides an unambiguous causal link between a gene locus and a phenotype. Traditionally, this has been used to identify genes for particular diseases. But, genetics can be used to transcend mere correlations and establish causal links between phenotypes and diseases.