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

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Abstract
The discovery of a gene newly implicated in the pathogenesis of type 1 diabetes may boost the development of predictive tests. A genome-wide association study on DNA from more than 500 patients with type 1 diabetes confirms associations with known type-1-diabetes-related genes and a new link to the KIAA0350 gene. This encodes a sugar-binding C-type lectin, one of a group of proteins whose functions include carbohydrate recognition and cell adhesion. Type 1 diabetes poses an increasing health problem, and clearly results from both genetic and environmental factors. A genome-wide association study has identified at least one gene, previously unexamined in diabetes, which should be followed up in future studies. Type 1 diabetes (T1D) in children results from autoimmune destruction of pancreatic beta cells, leading to insufficient production of insulin1. A number of genetic determinants of T1D have already been established through candidate gene studies, primarily within the major histocompatibility complex2,3,4 but also within other loci5,6,7,8,9,10,11,12. 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 loci2,3,4,5,6,7,8,9, 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.