ArticleProceedings of the National Academy of Sciences of the United States of America2006
Extreme genetic risk for type 1A diabetes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers, 4 of them syntheses that pooled it.
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Who cites it
100 citing papers in PubMed, 4 syntheses or guidelines pooled it, 251 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
- Systematic Review of Polygenic Risk Scores for Type 1 and Type 2 Diabetes.International journal of molecular sciences · 2020Pooled it
- ISPAD Clinical Practice Consensus Guidelines 2018: Definition, epidemiology, and classification of diabetes in children and adolescents.Pediatric diabetes · 2018Guideline
- HLA class II sequence variants influence tuberculosis risk in populations of European ancestry.Nature genetics · 2016Pooled it
- Identical and Nonidentical Twins: Risk and Factors Involved in Development of Islet Autoimmunity and Type 1 Diabetes.Diabetes care · 2019Trial
- Profiles of epigenetic histone post-translational modifications at type 1 diabetes susceptible genes.The Journal of biological chemistry · 2012Trial
- Trial
- Personalized medicine as a novel therapeutic approach for autoimmune diseases: new insights and future prospects.Osong public health and research perspectives · 2026Article
- Synthetic Immunological Niche Reveals Early Immune Dysregulation and Stratifies Therapeutic Response in Type 1 Diabetes.bioRxiv : the preprint server for biology · 2026Article
- Identification of a type 1 diabetes-associated T cell receptor repertoire signature from the human peripheral blood.Science advances · 2026Article
- Monogenic disorders of immunity: Common variants are not so rare.Cell genomics · 2026Review
- The inflammatory path toward type 1 diabetes begins during pregnancy.Nature communications · 2026Article
- Quantitative and large-scale investigation of human TCR-HLA cross-reactivity.Science advances · 2025Article
- Diabetes mellitus polygenic risk scores: heterogeneity and clinical translation.Nature reviews. Endocrinology · 2025Review
- Scaffold-free endocrine tissue engineering: role of islet organization and implications in type 1 diabetes.BMC endocrine disorders · 2025Review
- T helper 17 cells and interleukin-17 immunity in type 1 diabetes: From pathophysiology to targeted immunotherapies.World journal of diabetes · 2025Review
- Pre-Type 1 Diabetes in Adolescents and Teens: Screening, Nutritional Interventions, Beta-Cell Preservation, and Psychosocial Impacts.Journal of clinical medicine · 2025Review
- Population genetic dissection of HLA-DPB1 amino acid polymorphism to infer selection.Human immunology · 2024Article
- Natural Selection on HLA-DPB1 Amino Acids Operates Primarily on DP Serologic Categories.Human immunology · 2024Article
- Hailey-Hailey Disease is Associated with Diabetes: A Population-based Cohort Study, Clinical Cohort Study, and Pedigree Analysis.Acta dermato-venereologica · 2023Article
40 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
Type 1A diabetes (T1D) is an autoimmune disorder the risk of which is increased by specific HLA DR/DQ alleles [e.g., DRB1*03-DQB1*0201 (DR3) or DRB1*04-DQB1*0302 (DR4)]. The genotype associated with the highest risk for T1D is the DR3/4-DQ8 (DQ8 is DQA1*0301, DQB1*0302) heterozygous genotype. We determined HLA-DR and -DQ genotypes at birth and analyzed DR3/4-DQ8 siblings of patients with T1D for identical-by-descent HLA haplotype sharing (the number of haplotypes inherited in common between siblings). The children were clinically followed with prospective measurement of anti-islet autoimmunity and for progression to T1D. Risk for islet autoimmunity dramatically increased in DR3/4-DQ8 siblings who shared both HLA haplotypes with their diabetic proband sibling (63% by age 7, and 85% by age 15) compared with siblings who did not share both HLA haplotypes with their diabetic proband sibling (20% by age 15, P < 0.01). 55% sharing both HLA haplotypes developed diabetes by age 12 versus 5% sharing zero or one haplotype (P = 0.03). Despite sharing both HLA haplotypes with their proband, siblings without the HLA DR3/4-DQ8 genotype had only a 25% risk for T1D by age 12. The risk for T1D in the DR3/4-DQ8 siblings sharing both HLA haplotypes with their proband is remarkable for a complex genetic disorder and provides evidence that T1D is inherited with HLA-DR/DQ alleles and additional MHC-linked genes both determining major risk. A subset of siblings at extremely high risk for T1D can now be identified at birth for trials to prevent islet autoimmunity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.