A genome-wide association study identifies KIAA0350 as a type 1 diabetes gene

作者：Hakonarson Hakon^*; Grant Struan F A; Bradfield Jonathan P; Marchand Luc; Kim Cecilia E; Glessner Joseph T; Grabs Rosemarie; Casalunovo Tracy; Taback Shayne P; Frackelton Edward C; Lawson Margaret L; Robinson Luke J; Skraban Robert; Lu Yang; Chiavacci Rosetta M; Stanley Charles A; Kirsch Susan E; Rappaport Eric F; Orange Jordan S; Monos Dimitri S; Devoto Marcella; Qu Hui Qi; Polychronakos Constantin

来源：Nature, 2007, 448(7153): 591-U7.

DOI：10.1038/nature06010

Type 1 diabetes (T1D) in children results from autoimmune destruction of pancreatic beta cells, leading to insufficient production of insulin(1). A number of genetic determinants of T1D have already been established through candidate gene studies, primarily within the major histocompatibility complex(2-4) but also within other loci(5-12). To identify new genetic factors that increase the risk of T1D, we performed a genome-wide association study in a large paediatric cohort of European descent. In addition to confirming previously identified loci(2-9), we found that T1D was significantly associated with variation within a 233-kb linkage disequilibrium block on chromosome 16p13. This region contains KIAA0350, the gene product of which is predicted to be a sugar-binding, C-type lectin. Three common non-coding variants of the gene (rs2903692, rs725613 and rs17673553) in strong linkage disequilibrium reached genome-wide significance for association with T1D. A subsequent transmission disequilibrium test replication study in an independent cohort confirmed the association. These results indicate that KIAA0350 might be involved in the pathogenesis of T1D and demonstrate the utility of the genome-wide association approach in the identification of previously unsuspected genetic determinants of complex traits.

• 出版日期2007-8-2