Cellular and animal models of type 2 diabetes GWAS gene polymorphisms: what can we learn?

•Genome-wide association studies have identified ∼65 genomic loci associated with type 2 diabetes.•Gene inactivation or over-expression studies in cellular and murine models are revealing the actions of the identified genes including Tcf7l2, SLC30A8, CDKAL1 and others.

Genome-wide association studies (GWAS) have revealed multiple loci associated with increased type 2 diabetes (T2D) risk. Genes in the affected loci are likely therefore to play a role in disease aetiology, and may ultimately provide targets for intervention. The majority of identified polymorphisms alter insulin production, and often lie between or within several known genes. Determining which gene(s) contribute(s) to disease risk is likely to require complementary human, animal and cellular studies. Here I compare existing models for two of the most-studied GWAS-identified T2D risk genes, Tcf7l2 and ZnT8 (SLC30A8) and discuss prospects for examining other variants.