Patterson CC, Karuranga S, Salpea P, Saeedi P, Dahlquist G, Soltesz G et al. Worldwide estimates of incidence, prevalence and mortality of type 1 diabetes in children and adolescents: Results from the International Diabetes Federation Diabetes Atlas. Diabetes Res Clin Pract. 2019;157:107842.

Article  PubMed  Google Scholar 

Green A, Hede SM, Patterson CC, Wild SH, Imperatore G, Roglic G, et al. Type 1 diabetes in 2017: global estimates of incident and prevalent cases in children and adults. Diabetologia. 2021;64:2741–50.

Article  PubMed  PubMed Central  Google Scholar 

Leete P, Mallone R, Richardson SJ, Sosenko JM, Redondo MJ, Evans-Molina C. The effect of age on the progression and severity of type 1 diabetes: potential effects on disease mechanisms. Curr diabetes Rep. 2018;18:1–8.

Article  CAS  Google Scholar 

Rakyan VK, Beyan H, Down TA, Hawa MI, Maslau S, Aden D, et al. Identification of Type 1 Diabetes– Associated DNA Methylation Variable Positions That Precede Disease Diagnosis. PLOS Genet. 2011;7:e1002300.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kumar D, Gemayel NS, Deapen D, Kapadia D, Yamashita PH, Lee M, et al. North- American twins with IDDM. Genetic, etiological, and clinical significance of disease concordance according to age, zygosity, and the interval after diagnosis in first twin. Diabetes. 1993;42:1351–63.

Article  CAS  PubMed  Google Scholar 

Olmos P, A’Hern R, Heaton DA, Millward BA, Risley D, Pyke DA et al. The significance of the concordance rate for type 1 diabetes in identical twins. Diabetologia. 1988;31:747–50.

Kyvik KO, Green A, Beck-Nielsen H. Concordance rates of insulin dependent diabetes mellitus: a population based study of young Danish twins. BMJ. 1995;311:913–7.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hyttinen V, Kaprio J, Kinnunen L, Koskenvuo M, Tuomilehto J. Genetic liability of type 1 diabetes and the onset age among 22,650 young Finnish twin pairs: a nationwide follow-up study. Diabetes. 2003;52:1052–5.

Article  CAS  PubMed  Google Scholar 

Nerup J, Platz P, Andersen OO, Christy M, Lyngsoe J, Poulsen JE, et al. HL-A antigens and diabetes mellitus. Lancet Lond Engl. 1974;2:864–6.

Article  CAS  Google Scholar 

Bell GI, Horita S, Karam JH. A polymorphic locus near the human insulin gene is associated with insulin- dependent diabetes mellitus. Diabetes. 1984;33:176–83.

Article  CAS  PubMed  Google Scholar 

Barrett JC, Clayton DG, Concannon P, Akolkar B, Cooper JD, Erlich HA, et al. Genome-wide association study and meta- analysis find that over 40 loci affect risk of type 1 diabetes. Nate Genet. 2009;41:703–7.

Article  CAS  Google Scholar 

Bradfield JP, Qu HQ, Wang K, Zhang H, Sleiman PM, Kim CE, et al. A genome-wide meta-analysis of six type 1 diabetes cohorts identifies multiple associated loci. PLoS Genet. 2011;7:e1002293.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Onengut-Gumuscu S, Chen WM, Burren O, Cooper NJ, Quinlan AR, Mychaleckyj JC, et al. Fine mapping of type 1 diabetes susceptibility loci and evidence for colocalization of causal variants with lymphoid gene enhancers. Nat Genet. 2015;47:381–6.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Virgin HW, Todd JA. Metagenomics and personalized medicine. Cell. 2011;147:44–56.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Inshaw JRJ, Cutler AJ, Burren OS, Stefana MI, Todd JA. Approaches and advances in the genetic causes of autoimmune disease and their implications. Nat Immunol. 2018;19:674–84.

Article  CAS  PubMed  Google Scholar 

Caillat-Zucman S, Garchon HJ, Timsit J, Assan R, Boitard C, Djilali-Saiah I et al. Age- dependent HLA genetic heterogeneity of type 1 insulin-dependent diabetes mellitus. J Clin Invest. 1992;90:2242–50.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Howson JMM, Cooper JD, Smyth DJ, Walker NM, Stevens H, She JX, et al. Evidence of Gene-Gene Interaction and Age-at-Diagnosis Effects in Type 1 Diabetes. Diabetes. 2012;61:3012–7.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Inshaw JRJ, Cutler AJ, Crouch DJM, Wicker LS, Todd JA. 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. 2020;43:169–77.

Article  CAS  PubMed  Google Scholar 

Syreeni A, Sandholm N, Sidore C, Cucca F, Haukka J, Harjutsalo V, et al. Genome-wide search for genes affecting the age at diagnosis of type 1 diabetes. J Intern Med. 2021;289:662–74.

Article  CAS  PubMed  Google Scholar 

Moffatt MF, Gut IG, Demenais F, Strachan DP, Bouzigon E, Heath S, et al. A large-scale, consortium-based genomewide association study of asthma. N Engl J Med. 2010;363:1211–21.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhou Y, Zhou B, Pache L, Chang M, Khodabakhshi AH, Tanaseichuk O, et al. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat Commun. 2019;10:1523.

Article  PubMed  PubMed Central  Google Scholar 

Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003;11:2498–504.

Article  Google Scholar 

Piñero J, Bravo À, Queralt-Rosinach N, Gutiérrez-Sacristán A, Deu-Pons J, Centeno E, et al. DisGeNET: a comprehensive platform integrating information on human disease-associated genes and variants. Nucleic acids Res. 2017;45:D833–D839.

Article  PubMed  Google Scholar 

Benjamini Y, Hochberg Y. Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing. J R Stat Soc Ser B Methodol. 1995;57:289–300.

Article  Google Scholar 

Kieleväinen V, Turtinen M, Luopajärvi K, Härkönen T, Ilonen J, Knip M, et al. Increased HLA class II risk is associated with a more aggressive presentation of clinical type 1 diabetes. Acta Paediatr. 2023;112:522–8.

Article  PubMed  Google Scholar 

Pöllänen PM, Lempainen J, Laine AP, Toppari J, Veijola R, Vähäsalo P, et al. Characterisation of rapid progressors to type 1 diabetes among children with HLA-conferred disease susceptibility. Diabetologia. 2017;60:1284–93.

Article  PubMed  Google Scholar 

Bougnères P, Valleron AJ. Causes of early-onset type 1 diabetes: toward data-driven environmental approaches. J Exp Med. 2008;205:2953–7.

Article  PubMed  PubMed Central  Google Scholar 

Bougnères P, LeFur S, Valleron AJ. Early varicella infection is associated with a delayed onset of childhood type 1 diabetes. Diabetes Metabol. 2022;48:101394.

Verlaan DJ, Berlivet S, Hunninghake GM, Madore AM, Larivière M, Moussette S, et al. Allele-Specific Chromatin Remodeling in the ZPBP2/GSDMB/ORMDL3 Locus Associated with the Risk of Asthma and Autoimmune Disease. Am J Hum Genet. 2009;85:377–93.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kochi Y, Yamada R, Suzuki A, Harley JB, Shirasawa S, Sawada T, et al. A functional variant in FCRL3, encoding Fc receptor-like 3, is associated with rheumatoid arthritis and several autoimmunities. Nat Genet. 2005;37:478–85.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Eskdale J, McNicholl J, Wordsworth P, Jonas B, Huizinga T, Field M, et al. Interleukin-10 microsatellite polymorphisms and IL-10 locus alleles in rheumatoid arthritis susceptibility. Lancet. 1998;352:1282–3.

Article  CAS  PubMed  Google Scholar 

Lin YJ, Wan L, Sheu JJC, Huang CM, Lin CW, Lan YC, et al. G/T polymorphism in the interleukin-2 exon 1 region among Han Chinese systemic lupus erythematosus patients in Taiwan. Clin Immunol. 2008;129:36–9.

Article  CA