Can Non-HLA Single Nucleotide Polymorphisms Help Stratify Risk in TrialNet Relatives at Risk for Type 1 Diabetes?

The Journal of Clinical Endocrinology and Metabolism
Andrea K SteckType 1 Diabetes TrialNet Study Group

Abstract

Genome-wide association studies identified >50 type 1 diabetes (T1D) associated non-human leukocyte antigens (non-HLA) loci. The purpose of this study was to assess the contribution of non-HLA single nucleotide polymorphisms (SNPs) to risk of disease progression. The TrialNet Pathway to Prevention Study follows relatives of T1D patients for development of autoantibodies (Abs) and T1D. Using the Immunochip, we analyzed 53 diabetes-associated, non-HLA SNPs in 1016 Ab-positive, at-risk non-Hispanic white relatives. Effect of SNPs on the development of multiple Abs and T1D. Cox proportional analyses included all substantial non-HLA SNPs, HLA genotypes, relationship to proband, sex, age at initial screening, initial Ab type, and number. Factors involved in progression from single to multiple Abs included age at screening, relationship to proband, HLA genotypes, and rs3087243 (cytotoxic T lymphocyte antigen-4). Significant factors for diabetes progression included age at screening, Ab number, HLA genotypes, rs6476839 [GLIS family zinc finger 3 (GLIS3)], and rs3184504 [SH2B adaptor protein 3 (SH2B3)]. When glucose area under the curve (AUC) was included, factors involved in disease progression included glucose AUC, age at screening, A...Continue Reading

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Citations

Jun 21, 2019·Current Opinion in Endocrinology, Diabetes, and Obesity·Richard A Oram, Maria J Redondo
Jun 7, 2019·Diabetes Care·Maria J RedondoJay Sosenko
Jun 23, 2018·Diabetologia·Mustafa TosurUNKNOWN Type 1 Diabetes TrialNet Study Group
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Jul 8, 2021·Scientific Reports·Denis M NyagaJustin M O'Sullivan

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