Gene variants influencing measures of inflammation or predisposing to autoimmune and inflammatory diseases are not associated with the risk of type 2 diabetes.

AIMS/HYPOTHESIS: There are strong associations between measures of inflammation and type 2 diabetes, but the causal directions of these associations are not known. We tested the hypothesis that common gene variants known to alter circulating levels of inflammatory proteins, or known to alter autoimmune-related disease risk, influence type 2 diabetes risk. METHODS: We selected 46 variants: (1) eight variants known to alter circulating levels of inflammatory proteins, including those in the IL18, IL1RN, IL6R, MIF, PAI1 (also known as SERPINE1) and CRP genes; and (2) 38 variants known to predispose to autoimmune diseases, including type 1 diabetes. We tested the associations of these variants with type 2 diabetes using a meta-analysis of 4,107 cases and 5,187 controls from the Wellcome Trust Case Control Consortium, the Diabetes Genetics Initiative, and the Finland-United States Investigation of NIDDM studies. We followed up associated variants (p < 0.01) in a further set of 3,125 cases and 3,596 controls from the UK. RESULTS: We found no evidence that inflammatory or autoimmune disease variants are associated with type 2 diabetes (at p

What will whole genome searches for susceptibility genes for common complex disease offer to clinical practice?

In the developed world the majority of disease results from common, but complex disorders such as diabetes, obesity and cancer. Genetic variation explains a large proportion of an individual's risk of developing these diseases; however, success in identifying the particular gene variants involved has been limited. Recent advances in high-throughput genotyping technology, and a better understanding of the genetic architecture of complex disease has led to the development of genome-wide association studies (GWA), which are providing novel and important insights into disease processes. The results from these studies could be of substantial clinical importance in the relatively near future. In this review, we present some recent, exciting findings from studies that have used the GWA approach, and discuss the clinical application of identifying disease susceptibility genes and variants.