Parent-offspring trios - A resource to facilitate the identification of type 2 diabetes genes

The transmission disequilibrium test with use of trios (an affected proband with both parents) is a robust method for assessing the role of gene varia nts in disease that avoids the problem of population stratification that ma y confound conventional case/control studies and allows the detection of pa rent-of-origin effects. Trios have played a major role in defining genes in a number of polygenic conditions, including type I diabetes. We assessed t he prevalence, clinical characteristics, and suitability for defining type 2 susceptibility genes of European type 2 diabetes trios. In a Caucasian po pulation in the U.K., only 2.5% of type 2 patients had both parents alive. Using a nationwide strategy, we collected 182 trios defined by strict clini cal criteria. Immunological and genetic testing resulted in the exclusion o f 25 trios as a result of latent autoimmune diabetes (n = 13), inconsistent family relationships (n = 7), and maternally inherited diabetes and deafne ss (n = 5), The 157 remaining probands had similar treatment requirements t o familial type 2 diabetic subjects but presented at a younger age, were mo re obese, and more frequently had affected parents, Using this resource, we have not found any evidence for linkage disequilibrium between type 2 diab etes and the glucokinase gene markers GCK1 and GGK2 and the chromosome 20 m arker D20S197, We conclude that European type 2 diabetes trios are difficul t to collect but provide an important additional approach to dissecting the genetics of type 2 diabetes.