ArticlePLoS medicine2018
Genetic scores to stratify risk of developing multiple islet autoantibodies and type 1 diabetes: A prospective study in children.
Article in PLoS medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers, 3 of them syntheses that pooled it.
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Who cites it
103 citing papers in PubMed, 3 syntheses or guidelines pooled it, 143 citations in OpenAlex.
- ISPAD Clinical Practice Consensus Guidelines 2024: Screening, Staging, and Strategies to Preserve Beta-Cell Function in Children and Adolescents with Type 1 Diabetes.Hormone research in paediatrics · 2024Guideline
- Sodium-glucose cotransporter inhibitors as add-on therapy in addition to insulin for type 1 diabetes mellitus: A meta-analysis of randomized controlled trials.Journal of diabetes investigation · 2021Pooled it
- Systematic Review of Polygenic Risk Scores for Type 1 and Type 2 Diabetes.International journal of molecular sciences · 2020Pooled it
- Feasibility of Fast Turnaround Genetic Screening for Type 1 Diabetes Risk in Newborns - Recruiting Infants for the Global Platform for the Prevention of Autoimmune Diabetes Primary Prevention Study Supplementation with B ifidobacterium infantis for Mitigation of Type 1 Diabetes Autoimmunity.Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme · 2026Trial
- Identification of infants with increased type 1 diabetes genetic risk for enrollment into Primary Prevention Trials-GPPAD-02 study design and first results.Pediatric diabetes · 2019Trial
- Predicting future risk of type 1 and type 2 diabetes after gestational diabetes mellitus using polygenic scores: a cohort study.Diabetologia · 2026Observational
- International consensus guidance for general population screening for islet autoantibodies to diagnose early-stage type 1 diabetes: a nominal group technique process.Diabetologia · 2026Article
- Determinants of Infant Participation and Non-Participation in Primary Prevention Trials.Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme · 2026Article
- Preimplantation genetic testing for polygenic diseases: A novel paradigm in embryo selection.Biochemistry and biophysics reports · 2026Review
- Enhancing Type 1 Diabetes Polygenic Risk Prediction Through Neural Networks and Entropy-Derived Insights.International journal of molecular sciences · 2026Article
- Health care providers' perceptions of screening for risk of type 1 diabetes in newborns using genetic risk scores.Journal of community genetics · 2026Article
- Article
- Genetic Risk and Transition Through Preclinical Stages of Type 1 Diabetes.The Journal of clinical endocrinology and metabolism · 2026Article
- Type 1 Diabetes and Other Autoimmune Diseases-Epidemiology, Pathophysiology and Screening.Endocrinology, diabetes & metabolism · 2026Review
- Polygenic score from MODY genes is associated with type 1 diabetes and disease characteristics.Acta diabetologica · 2025Article
- Preclinical Diagnosis of Type 1 Diabetes: Reality or Utopia.Biomedicines · 2025Review
- Inhibition of pyrimidine de novo synthesis fosters Treg cells and reduces diabetes development in models of Type 1 Diabetes.Molecular metabolism · 2025Article
- Diabetes mellitus polygenic risk scores: heterogeneity and clinical translation.Nature reviews. Endocrinology · 2025Review
- Type 1 diabetes prediction in autoantibody-positive individuals: performance, time and money matter.Diabetologia · 2025Article
- Type 1 diabetes risk factors, risk prediction and presymptomatic detection: Evidence and guidance for screening.Diabetes, obesity & metabolism · 2025Review
43 more citing papers are in PubMed but not listed here.
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Authors and funding
22 authors at 13 institutions in 6 countries.
Funding
Abstract
backgroundAround 0.3% of newborns will develop autoimmunity to pancreatic beta cells in childhood and subsequently develop type 1 diabetes before adulthood. Primary prevention of type 1 diabetes will require early intervention in genetically at-risk infants. The objective of this study was to determine to what extent genetic scores (two previous genetic scores and a merged genetic score) can improve the prediction of type 1 diabetes. METHODS AND
findingsThe Environmental Determinants of Diabetes in the Young (TEDDY) study followed genetically at-risk children at 3- to 6-monthly intervals from birth for the development of islet autoantibodies and type 1 diabetes. Infants were enrolled between 1 September 2004 and 28 February 2010 and monitored until 31 May 2016. The risk (positive predictive value) for developing multiple islet autoantibodies (pre-symptomatic type 1 diabetes) and type 1 diabetes was determined in 4,543 children who had no first-degree relatives with type 1 diabetes and either a heterozygous HLA DR3 and DR4-DQ8 risk genotype or a homozygous DR4-DQ8 genotype, and in 3,498 of these children in whom genetic scores were calculated from 41 single nucleotide polymorphisms. In the children with the HLA risk genotypes, risk for developing multiple islet autoantibodies was 5.8% (95% CI 5.0%-6.6%) by age 6 years, and risk for diabetes by age 10 years was 3.7% (95% CI 3.0%-4.4%). Risk for developing multiple islet autoantibodies was 11.0% (95% CI 8.7%-13.3%) in children with a merged genetic score of >14.4 (upper quartile; n = 907) compared to 4.1% (95% CI 3.3%-4.9%, P < 0.001) in children with a genetic score of ≤14.4 (n = 2,591). Risk for developing diabetes by age 10 years was 7.6% (95% CI 5.3%-9.9%) in children with a merged score of >14.4 compared with 2.7% (95% CI 1.9%-3.6%) in children with a score of ≤14.4 (P < 0.001). Of 173 children with multiple islet autoantibodies by age 6 years and 107 children with diabetes by age 10 years, 82 (sensitivity, 47.4%; 95% CI 40.1%-54.8%) and 52 (sensitivity, 48.6%, 95% CI 39.3%-60.0%), respectively, had a score >14.4. Scores were higher in European versus US children (P = 0.003). In children with a merged score of >14.4, risk for multiple islet autoantibodies was similar and consistently >10% in Europe and in the US; risk was greater in males than in females (P = 0.01). Limitations of the study include that the genetic scores were originally developed from case-control studies of clinical diabetes in individuals of mainly European decent. It is, therefore, possible that it may not be suitable to all populations.
conclusionsA type 1 diabetes genetic score identified infants without family history of type 1 diabetes who had a greater than 10% risk for pre-symptomatic type 1 diabetes, and a nearly 2-fold higher risk than children identified by high-risk HLA genotypes alone. This finding extends the possibilities for enrolling children into type 1 diabetes primary prevention trials.
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