title: Evidence of stage- and age-related heterogeneity of non-HLA SNPs and risk of islet autoimmunity and type 1 diabetes: the diabetes autoimmunity study in the young.
abstract: Previously, we examined 20 non-HLA SNPs for association with islet autoimmunity (IA) and/or progression to type 1 diabetes (T1D). Our objective was to investigate fourteen additional non-HLA T1D candidate SNPs for stage- and age-related heterogeneity in the etiology of T1D. Of 1634 non-Hispanic white DAISY children genotyped, 132 developed IA (positive for GAD, insulin, or IA-2 autoantibodies at two or more consecutive visits); 50 IA positive children progressed to T1D. Cox regression was used to analyze risk of IA and progression to T1D in IA positive children. Restricted cubic splines were used to model SNPs when there was evidence that risk was not constant with age. C1QTNF6 (rs229541) predicted increased IA risk (HR: 1.57, CI: 1.20-2.05) but not progression to T1D (HR: 1.13, CI: 0.75-1.71). SNP (rs10517086) appears to exhibit an age-related effect on risk of IA, with increased risk before age 2 years (age 2 HR: 1.67, CI: 1.08-2.56) but not older ages (age 4 HR: 0.84, CI: 0.43-1.62). C1QTNF6 (rs229541), SNP (rs10517086), and UBASH3A (rs3788013) were associated with development of T1D. This prospective investigation of non-HLA T1D candidate loci shows that some SNPs may exhibit stage- and age-related heterogeneity in the etiology of T1D.
authors.affiliation: Colorado School of Public Health, University of Colorado, 13001 E. 17th Place, Box B119, Aurora, CO 80045, USA.
authors.forename: Brittni N
authors.initials: BN
authors.lastname: Frederiksen
authors.affiliation: Barbara Davis Center for Childhood Diabetes, University of Colorado, 1775 Aurora Ct., Aurora, CO 80045, USA.
authors.forename: Andrea K
authors.initials: AK
authors.lastname: Steck
authors.affiliation: Colorado School of Public Health, University of Colorado, 13001 E. 17th Place, Box B119, Aurora, CO 80045, USA.
authors.forename: Miranda
authors.initials: M
authors.lastname: Kroehl
authors.affiliation: Colorado School of Public Health, University of Colorado, 13001 E. 17th Place, Box B119, Aurora, CO 80045, USA.
authors.forename: Molly M
authors.initials: MM
authors.lastname: Lamb
authors.affiliation: Barbara Davis Center for Childhood Diabetes, University of Colorado, 1775 Aurora Ct., Aurora, CO 80045, USA.
authors.forename: Randall
authors.initials: R
authors.lastname: Wong
authors.affiliation: Barbara Davis Center for Childhood Diabetes, University of Colorado, 1775 Aurora Ct., Aurora, CO 80045, USA.
authors.forename: Marian
authors.initials: M
authors.lastname: Rewers
authors.affiliation: Colorado School of Public Health, University of Colorado, 13001 E. 17th Place, Box B119, Aurora, CO 80045, USA.
authors.forename: Jill M
authors.initials: JM
authors.lastname: Norris
mesh_terms: D000293:Adolescent; D000367:Age Factors; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D015551:Autoimmunity / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology*; D018450:Disease Progression; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology*; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D001323:Autoantibodies; D006680:HLA Antigens