The Environmental Determinants of Diabetes in the Young (TEDDY) study prospectively follows 8,677 children enrolled from birth who carry HLA-susceptibility genotypes for development of islet autoantibodies (IA) and type 1 diabetes (T1D). During the median follow-up time of 57 months, 350 children developed at least one persistent IA (GAD antibody, IA-2A, or micro insulin autoantibodies) and 84 of them progressed to T1D. We genotyped 5,164 Caucasian children for 41 non-HLA single nucleotide polymorphisms (SNPs) that achieved genome-wide significance for association with T1D in the genome-wide association scan meta-analysis conducted by the Type 1 Diabetes Genetics Consortium. In TEDDY participants carrying high-risk HLA genotypes, eight SNPs achieved significant association to development of IA using time-to-event analysis (P < 0.05), whereof four were significant after adjustment for multiple testing (P < 0.0012): rs2476601 in PTPN22 (hazard ratio [HR] 1.54 [95% CI 1.27-1.88]), rs2292239 in ERBB3 (HR 1.33 [95% CI 1.14-1.55]), rs3184504 in SH2B3 (HR 1.38 [95% CI 1.19-1.61]), and rs1004446 in INS (HR 0.77 [0.66-0.90]). These SNPs were also significantly associated with T1D in particular: rs2476601 (HR 2.42 [95% CI 1.70-3.44]). Al...Continue Reading
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Effects of non-HLA gene polymorphisms on development of islet autoimmunity and type 1 diabetes in a population with high-risk HLA-DR,DQ genotypes
Effect of the PTPN22 and INS risk genotypes on the progression to clinical type 1 diabetes after the initiation of β-cell autoimmunity
The putative role of the C1858T polymorphism of protein tyrosine phosphatase PTPN22 gene in autoimmunity
Characteristics of rapid vs slow progression to type 1 diabetes in multiple islet autoantibody-positive children.
A strategy to find gene combinations that identify children who progress rapidly to type 1 diabetes after islet autoantibody seroconversion
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
A Type 1 Diabetes Genetic Risk Score Can Aid Discrimination Between Type 1 and Type 2 Diabetes in Young Adults
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Non-HLA gene effects on the disease process of type 1 diabetes: From HLA susceptibility to overt disease
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Genetic scores to stratify risk of developing multiple islet autoantibodies and type 1 diabetes: A prospective study in children.
Maternal dietary supplement use and development of islet autoimmunity in the offspring: TEDDY study.
Predicting progression to type 1 diabetes from ages 3 to 6 in islet autoantibody positive TEDDY children.
HLA-DPB1*04:01 Protects Genetically Susceptible Children from Celiac Disease Autoimmunity in the TEDDY Study.
Application of a Genetic Risk Score to Racially Diverse Type 1 Diabetes Populations Demonstrates the Need for Diversity in Risk-Modeling.
Genetic Contribution to the Divergence in Type 1 Diabetes Risk Between Children From the General Population and Children From Affected Families.
Variants in the BACH2 and CLEC16A gene might be associated with susceptibility to insulin-triggered type 1 diabetes
Progression from islet autoimmunity to clinical type 1 diabetes is influenced by genetic factors: results from the prospective TEDDY study.
Respiratory infections are temporally associated with initiation of type 1 diabetes autoimmunity: the TEDDY study.
Pandemrix® vaccination is not associated with increased risk of islet autoimmunity or type 1 diabetes in the TEDDY study children
Hierarchical Order of Distinct Autoantibody Spreading and Progression to Type 1 Diabetes in the TEDDY Study.
Complement gene variants in relation to autoantibodies to beta cell specific antigens and type 1 diabetes in the TEDDY Study.
Genetic and Environmental Interactions Modify the Risk of Diabetes-Related Autoimmunity by 6 Years of Age: The TEDDY Study.
C1858T Polymorphism of Protein Tyrosine Phosphatase Non-receptor Type 22 (PTPN22): an eligible target for prevention of type 1 diabetes?
Analgesic antipyretic use among young children in the TEDDY study: no association with islet autoimmunity.
The Influence of Type 1 Diabetes Genetic Susceptibility Regions, Age, Sex, and Family History on the Progression From Multiple Autoantibodies to Type 1 Diabetes: A TEDDY Study Report.
Dual Role of PTPN22 but Not NLRP3 Inflammasome Polymorphisms in Type 1 Diabetes and Celiac Disease in Children
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