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- Title
Parent-offspring trios: a resource to facilitate the identification of type 2 diabetes genes.
- Authors
Frayling TM; Walker M; McCarthy MI; Evans JC; Allen LI; Lynn S; Ayres S; Millauer B; Turner C; Turner RC; Sampson MJ; Hitman GA; Ellard S; Hattersley AT; Frayling, T M; Walker, M; McCarthy, M I; Evans, J C; Allen, L I; Lynn, S
- Abstract
The transmission disequilibrium test with use of trios (an affected proband with both parents) is a robust method for assessing the role of gene variants in disease that avoids the problem of population stratification that may confound conventional case/control studies and allows the detection of parent-of-origin effects. Trios have played a major role in defining genes in a number of polygenic conditions, including type 1 diabetes. We assessed the prevalence, clinical characteristics, and suitability for defining type 2 susceptibility genes of European type 2 diabetes trios. In a Caucasian population 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 clinical criteria. Immunological and genetic testing resulted in the exclusion of 25 trios as a result of latent autoimmune diabetes (n = 13), inconsistent family relationships (n = 7), and maternally inherited diabetes and deafness (n = 5). The 157 remaining probands had similar treatment requirements to familial type 2 diabetic subjects but presented at a younger age, were more obese, and more frequently had affected parents. Using this resource, we have not found any evidence for linkage disequilibrium between type 2 diabetes and the glucokinase gene markers GCK1 and GCK2 and the chromosome 20 marker D20S197. We conclude that European type 2 diabetes trios are difficult to collect but provide an important additional approach to dissecting the genetics of type 2 diabetes.
- Publication
Diabetes, 1999, Vol 48, Issue 12, p2475
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/diabetes.48.12.2475