title: A genome-wide association study identifies KIAA0350 as a type 1 diabetes gene.
abstract: Type 1 diabetes (T1D) in children results from autoimmune destruction of pancreatic beta cells, leading to insufficient production of insulin. A number of genetic determinants of T1D have already been established through candidate gene studies, primarily within the major histocompatibility complex but also within other loci. 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, 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.
authors.affiliation: Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA. hakonarson@chop.edu
authors.forename: Hakon
authors.initials: H
authors.lastname: Hakonarson
authors.forename: Struan F A
authors.initials: SF
authors.lastname: Grant
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Bradfield
authors.forename: Luc
authors.initials: L
authors.lastname: Marchand
authors.forename: Cecilia E
authors.initials: CE
authors.lastname: Kim
authors.forename: Joseph T
authors.initials: JT
authors.lastname: Glessner
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Grabs
authors.forename: Tracy
authors.initials: T
authors.lastname: Casalunovo
authors.forename: Shayne P
authors.initials: SP
authors.lastname: Taback
authors.forename: Edward C
authors.initials: EC
authors.lastname: Frackelton
authors.forename: Margaret L
authors.initials: ML
authors.lastname: Lawson
authors.forename: Luke J
authors.initials: LJ
authors.lastname: Robinson
authors.forename: Robert
authors.initials: R
authors.lastname: Skraban
authors.forename: Yang
authors.initials: Y
authors.lastname: Lu
authors.forename: Rosetta M
authors.initials: RM
authors.lastname: Chiavacci
authors.forename: Charles A
authors.initials: CA
authors.lastname: Stanley
authors.forename: Susan E
authors.initials: SE
authors.lastname: Kirsch
authors.forename: Eric F
authors.initials: EF
authors.lastname: Rappaport
authors.forename: Jordan S
authors.initials: JS
authors.lastname: Orange
authors.forename: Dimitri S
authors.initials: DS
authors.lastname: Monos
authors.forename: Marcella
authors.initials: M
authors.lastname: Devoto
authors.forename: Hui-Qi
authors.initials: HQ
authors.lastname: Qu
authors.forename: Constantin
authors.initials: C
authors.lastname: Polychronakos
mesh_terms: D016022:Case-Control Studies; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D037181:Lectins, C-Type; D015810:Linkage Disequilibrium / Q000235:genetics; D009004:Monosaccharide Transport Proteins / Q000235:genetics*; D009679:Nuclear Family; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: C522505:CLEC16A protein, human; D005819:Genetic Markers; D037181:Lectins, C-Type; D009004:Monosaccharide Transport Proteins