The UK Type 2 diabetes genetics consortium case-control collection: a resource for the genetic epidemiology of Type 2 diabetes. (360G-Wellcome-072960_Z_03_Z)

Type 2 diabetes (T2D) is a major and increasing cause of morbidity and mortality worldwide. Familial, twin, admixture and migration studies all indicate a substantial contribution of genetic factors in the aetiology of this common complex disorder. Substantial advances in gene identification are now being made: linkage scans have highlighted consistently replicated regions harbouring susceptibility genes and a growing number of substantiated susceptibility variants have been defined. UK research has contributed to these findings using existing collaborative collections of familial T2D resources collected by the Diabetes UK (Warren 2) Type 2 Diabetes Genetics Consortium (1050 T2D sib pairs, 870 physiologically characterised 1° relatives, 540 parent-offspring trios). Further progress in definition and characterisation of these and novel genes will require a large community-based T2D case/control DNA resource, enriched by the availability of detailed long- term clinical follow-up. This resource will allow: study of the modest relative risks expected of many susceptibility variants, replication of other resources, measurement of the population attributable risk of susceptibility variants, evaluation of potential gene/gene and gene/environment interactions, definition of complication-related susceptibility variants, and exploration of genetic effects on treatment response. There is, therefore, a clear case to be made for establishing such a resource. In Tayside (population 400,000) all patients with diabetes have, since 1993, been registered on a comprehensive, validated database, featuring extensive record linkage to health care and patient specific, population-based prescribing activity, unparalleled in the UK. From this dynamic register, we will collect a total of 7,500 T2D cases, and through local GP practices, 7,500 population-based, age-matched, non- diabetic control subjects. With such a sample, we can expect to detect modest susceptibility effects (relative risks 1.2) with reasonable power (>80%) across a wide range of allele frequencies (<0.10 to ~0.90) even under stringent significance thresholds (p<0.0001). All resources for patient tagging, follow up, data collection and data validation are in place and fully-funded. The collection will be overseen, and access to the resource managed, by the UK Type 2 Diabetes Genetics Consortium.