ArticleDiabetes2012
Evidence of gene-gene interaction and age-at-diagnosis effects in type 1 diabetes.
Article in Diabetes, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
36 citing papers in PubMed, 2 syntheses or guidelines pooled it, 74 citations in OpenAlex.
- Association of genetic variation with age at diagnosis in type 1 diabetes.BMJ open diabetes research & care · 2026Pooled it
- Genome-wide search for genes affecting the age at diagnosis of type 1 diabetes.Journal of internal medicine · 2021Pooled it
- Relative maternal protection against type 1 diabetes: A combined analysis of 5 observational studies.The Journal of clinical endocrinology and metabolism · 2026Article
- Renalase inhibition defends against acute and chronic β cell stress by regulating cell metabolism.Molecular metabolism · 2025Article
- Genomic variants associated with age at diagnosis of childhood-onset type 1 diabetes.Journal of human genetics · 2024Article
- Research progress of autoimmune diseases based on induced pluripotent stem cells.Frontiers in immunology · 2024Review
- The rare DRB1*04:08-DQ8 haplotype is the main HLA class II genetic driver and discriminative factor of Early-onset Type 1 diabetes in the Portuguese population.Frontiers in immunology · 2023Article
- The missing heritability in type 1 diabetes.Diabetes, obesity & metabolism · 2022Review
- Single-cell multi-omics analysis of human pancreatic islets reveals novel cellular states in type 1 diabetes.Nature metabolism · 2022Article
- Renalase gene Glu37Asp polymorphism affects susceptibility to diabetic retinopathy in type 2 diabetes mellitus.Acta diabetologica · 2021Article
- Review
- Genome-scale in vivo CRISPR screen identifies RNLS as a target for beta cell protection in type 1 diabetes.Nature metabolism · 2020Article
- Genetic Variants Predisposing Most Strongly to Type 1 Diabetes Diagnosed Under Age 7 Years Lie Near Candidate Genes That Function in the Immune System and in Pancreatic β-Cells.Diabetes care · 2020Article
- Genetics of Type 1 Diabetes Comes of Age.Diabetes care · 2020Article
- The Effect of Age on the Progression and Severity of Type 1 Diabetes: Potential Effects on Disease Mechanisms.Current diabetes reports · 2018Review
- The Role of NOD Mice in Type 1 Diabetes Research: Lessons from the Past and Recommendations for the Future.Frontiers in endocrinology · 2018Article
- The chromosome 6q22.33 region is associated with age at diagnosis of type 1 diabetes and disease risk in those diagnosed under 5 years of age.Diabetologia · 2018Article
- The Genetic Architecture of Type 1 Diabetes.Genes · 2017Review
- Cohort Profile: Scottish Diabetes Research Network Type 1 Bioresource Study (SDRNT1BIO).International journal of epidemiology · 2017Article
- A method for identifying genetic heterogeneity within phenotypically defined disease subgroups.Nature genetics · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 11 institutions in 5 countries.
Funding
Abstract
The common genetic loci that independently influence the risk of type 1 diabetes have largely been determined. Their interactions with age-at-diagnosis of type 1 diabetes, sex, or the major susceptibility locus, HLA class II, remain mostly unexplored. A large collection of more than 14,866 type 1 diabetes samples (6,750 British diabetic individuals and 8,116 affected family samples of European descent) were genotyped at 38 confirmed type 1 diabetes-associated non-HLA regions and used to test for interaction of association with age-at-diagnosis, sex, and HLA class II genotypes using regression models. The alleles that confer susceptibility to type 1 diabetes at interleukin-2 (IL-2), IL2/4q27 (rs2069763) and renalase, FAD-dependent amine oxidase (RNLS)/10q23.31 (rs10509540), were associated with a lower age-at-diagnosis (P = 4.6 × 10⁻⁶ and 2.5 × 10⁻⁵, respectively). For both loci, individuals carrying the susceptible homozygous genotype were, on average, 7.2 months younger at diagnosis than those carrying the protective homozygous genotypes. In addition to protein tyrosine phosphatase nonreceptor type 22 (PTPN22), evidence of statistical interaction between HLA class II genotypes and rs3087243 at cytotoxic T-lymphocyte antigen 4 (CTLA4)/2q33.2 was obtained (P = 7.90 × 10⁻⁵). No evidence of differential risk by sex was obtained at any loci (P ≥ 0.01). Statistical interaction effects can be detected in type 1 diabetes although they provide a relatively small contribution to our understanding of the familial clustering of the disease.
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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.