Katsarou A, Gudbjörnsdottir S, Rawshani A, Dabelea D, Bonifacio E, Anderson BJ, et al. Type 1 diabetes mellitus. Nat Reviews Dis Primers. 2017;3(1):1–7.

Battaglia M, Ahmed S, Anderson MS, Atkinson MA, Becker D, Bingley PJ, et al. Introducing the endotype concept to address the challenge of disease heterogeneity in type 1 diabetes. Diabetes Care. 2020;43(1):5–12.

Article  PubMed  Google Scholar 

Greenbaum C, VanBuecken D, Lord S. Disease-modifying therapies in type 1 diabetes: a look into the future of diabetes practice. Drugs. 2019;79(1):43–61.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lehuen A, Diana J, Zaccone P, Cooke A. Immune cell crosstalk in type 1 diabetes. Nat Rev Immunol. 2010;10(7):501–13.

Article  CAS  PubMed  Google Scholar 

Eizirik DL, Szymczak F, Alvelos MI, Martin F. From pancreatic \(\beta\)-cell gene networks to novel therapies for type 1 diabetes. Diabetes. 2021;70(9):1915–25.

Mehdi AM, Hamilton-Williams EE, Cristino A, Ziegler A, Bonifacio E, Le Cao KA, et al. A peripheral blood transcriptomic signature predicts autoantibody development in infants at risk of type 1 diabetes. JCI Insight. 2018;3(5):e98212.

Kallionpää H, Elo LL, Laajala E, Mykkänen J, Ricaño-Ponce I, Vaarma M, et al. Innate immune activity is detected prior to seroconversion in children with HLA-conferred type 1 diabetes susceptibility. Diabetes. 2014;63(7):2402–14.

Article  PubMed  Google Scholar 

Cabrera SM, Chen YG, Hagopian WA, Hessner MJ. Blood-based signatures in type 1 diabetes. Diabetologia. 2016;59(3):414–25.

Article  CAS  PubMed  Google Scholar 

Xhonneux LP, Knight O, Lernmark Å, Bonifacio E, Hagopian WA, Rewers MJ, et al. Transcriptional networks in at-risk individuals identify signatures of type 1 diabetes progression. Sci Transl Med. 2021;13(587):eabd5666.

Walker LS, von Herrath M. CD4 T cell differentiation in type 1 diabetes. Clin Exp Immunol. 2016;183(1):16–29.

Article  CAS  PubMed  Google Scholar 

Danke NA, Koelle DM, Yee C, Beheray S, Kwok WW. Autoreactive T cells in healthy individuals. J Immunol. 2004;172(10):5967–72.

Article  CAS  PubMed  Google Scholar 

Kurien M, Mollazadegan K, Sanders DS, Ludvigsson JF. Celiac disease increases risk of thyroid disease in patients with type 1 diabetes: a nationwide cohort study. Diabetes Care. 2016;39(3):371–5.

Article  CAS  PubMed  Google Scholar 

Farh KKH, Marson A, Zhu J, Kleinewietfeld M, Housley WJ, Beik S, et al. Genetic and epigenetic fine mapping of causal autoimmune disease variants. Nature. 2015;518(7539):337–43.

Article  CAS  PubMed  Google Scholar 

Parker SC, Stitzel ML, Taylor DL, Orozco JM, Erdos MR, Akiyama JA, et al. Chromatin stretch enhancer states drive cell-specific gene regulation and harbor human disease risk variants. Proc Natl Acad Sci. 2013;110(44):17921–6.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Watanabe K, Mirkov MU, de Leeuw CA, van den Heuvel MP, Posthuma D. Genetic mapping of cell type specificity for complex traits. Nat Commun. 2019;10(1):1–13.

Article  Google Scholar 

Zhu Z, Zhang F, Hu H, Bakshi A, Robinson MR, Powell JE, et al. Integration of summary data from GWAS and eQTL studies predicts complex trait gene targets. Nat Genet. 2016;48(5):481–7.

Article  CAS  PubMed  Google Scholar 

Noble JA, Valdes AM. Genetics of the HLA region in the prediction of type 1 diabetes. Curr Diabetes Rep. 2011;11(6):533–42.

Article  CAS  Google Scholar 

Russell MA, Redick SD, Blodgett DM, Richardson SJ, Leete P, Krogvold L, et al. HLA class II antigen processing and presentation pathway components demonstrated by transcriptome and protein analyses of islet \(\beta\)-cells from donors with type 1 diabetes. Diabetes. 2019;68(5):988–1001.

Bonifacio E, Yu L, Williams AK, Eisenbarth GS, Bingley PJ, Marcovina SM, et al. Harmonization of glutamic acid decarboxylase and islet antigen-2 autoantibody assays for national institute of diabetes and digestive and kidney diseases consortia. J Clin Endocrinol Metab. 2010;95(7):3360–7.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Vehik K, Beam CA, Mahon JL, Schatz DA, Haller MJ, Sosenko JM, et al. Development of autoantibodies in the TrialNet natural history study. Diabetes Care. 2011;34(9):1897–901.

Article  PubMed  PubMed Central  Google Scholar 

Sosenko JM, Skyler JS, Palmer JP, Krischer JP, Yu L, Mahon J, et al. The prediction of type 1 diabetes by multiple autoantibody levels and their incorporation into an autoantibody risk score in relatives of type 1 diabetic patients. Diabetes Care. 2013;36(9):2615–20.

Article  PubMed  PubMed Central  Google Scholar 

Rahman AH, Homann D. Mass cytometry and type 1 diabetes research in the age of single-cell data science. Curr Opin Endocrinol Diabetes Obes. 2020;27(4):231–9.

Article  PubMed  PubMed Central  Google Scholar 

Chen YG, Cabrera SM, Jia S, Kaldunski ML, Kramer J, Cheong S, et al. Molecular signatures differentiate immune states in type 1 diabetic families. Diabetes. 2014;63(11):3960–73.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kallionpää H, Somani J, Tuomela S, Ullah U, De Albuquerque R, Lönnberg T, et al. Early detection of peripheral blood cell signature in children developing \(\beta\)-cell autoimmunity at a young age. Diabetes. 2019;68(10):2024–34.

Teniente-Serra A, Pizarro E, Quirant-Sánchez B, Fernández MA, Vives-Pi M, Martinez-Caceres EM. Identifying changes in peripheral lymphocyte subpopulations in adult onset type 1 diabetes. Front Immunol. 2021;12:784110.

Hippich M, Beyerlein A, Hagopian WA, Krischer JP, Vehik K, Knoop J, et al. Genetic contribution to the divergence in type 1 diabetes risk between children from the general population and children from affected families. Diabetes. 2019;68(4):847–57.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Inshaw JR, Cutler AJ, Crouch DJ, 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 \(\beta\)-cells. Diabetes Care. 2020;43(1):169–77.

Harsunen M, Kettunen JL, Härkönen T, Dwivedi O, Lehtovirta M, Vähäsalo P, et al. Identification of monogenic variants in more than ten per cent of children without type 1 diabetes-related autoantibodies at diagnosis in the Finnish Pediatric Diabetes Register. Diabetologia. 2023;66(3):438–49.

Article  CAS  PubMed  Google Scholar 

Fasolino M, Schwartz GW, Patil AR, Mongia A, Golson ML, Wang YJ, et al. Single-cell multi-omics analysis of human pancreatic islets reveals novel cellular states in type 1 diabetes. Nat Metab. 2022;4(2):284–99.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Howson JM, Rosinger S, Smyth DJ, Boehm BO, study group AE, Todd JA. Genetic analysis of adult-onset autoimmune diabetes. Diabetes. 2011;60(10):2645–53.

Ong Y, Koh W, Ng M, Tam ZY, Lim S, Boehm BO, et al. Glutamic acid decarboxylase and islet antigen 2 antibody profiles in people with adult-onset diabetes mellitus: a comparison between mixed ethnic populations in Singapore and Germany. Diabet Med. 2017;34(8):1145–53.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Dimitrov S, Benedict C, Heutling D, Westermann J, Born J, Lange T. Cortisol and epinephrine control opposing circadian rhythms in T cell subsets. Blood J Am Soc Hematol. 2009;113(21):5134–43.

CAS  Google Scholar 

Dimitrov S, Lange T, Nohroudi K, Born J. Number and function of circulating human antigen presenting cells regulated by sleep. Sleep. 2007;30(4):401–11.

Article  PubMed  Google Scholar 

Kronfol Z, Nair M, Zhang Q, Hill EE, Brown MB. Circadian immune measures in healthy volunteers: relationship to hypothalamic-pituitary-adrenal axis hormones and sympathetic neurotransmitters. Psychosom Med. 1997;59(1):42–50.

Article  CAS  PubMed  Google Scholar 

Rosinger S, Nutland S, Mickelson E, Varney MD, Boehm BO, Olsem GJ, et al. Collection and processing of whole blood for transformation of peripheral blood mononuclear cells and extraction of DNA: the Type 1 Diabetes Genetics Consortium. Clin Trials. 2010;7(1_suppl):S65–74.

Kimura A, Dong RP, Harada H, Sasazuki T. DNA typing of HLA class II genes in B-lymphoblastoid cell lines homozygous for HLA. Tissue Antigens. 1992;40(1):5–12.

Article  CAS  PubMed  Google Scholar 

Endl J, Rosinger S, Schwarz B, Friedrich SO, Rothe G, Karges W, et al. Coexpression of CD25 and OX40 (CD134) receptors delineates autoreactive T-cells in type 1 diabetes. Diabetes. 2006;55(1):50–60.

Article  CAS  PubMed  Google Scholar 

Strebelow M, Schlosser M, Ziegler B, Rjasanowski I, Ziegler M. Karlsburg Type I diabetes risk study of a general population: frequencies and interactions of the four major type I diabetes-associated autoantibodies studied in 9419 schoolchildren. Diabetologia. 1999;42(6):661–70.

Article  CAS  PubMed  Google Scholar 

Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet. 2007;81(3):559–75.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Danecek P, Auton A, Abecasis G, Albers CA, Banks E, DePristo MA, et al. The variant call format and VCFtools. Bioinformatics. 2011;27(15):2156–8.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Browning BL, Zhou Y, Browning SR. A one-penny imputed genome from next-generation reference panels. Am J Hum Genet. 2018;103(3):338–48.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kang HM, Subramaniam M, Targ S, Nguyen M, Maliskova L, McCarthy E, et al. Multiplexed droplet single-cell RNA-sequencing using natural genetic variation. Nat Biotechnol. 2018;36(1):89–94.

Article  CAS  PubMed  Google Scholar 

Butler A, Hoffman P, Smibert P, Papalexi E, Satija R. Integrating single-cell transcriptomic data across different conditions, technologies, and species. Nat Biotechnol. 2018;36(5):411–20.

Article  CAS  PubMed  PubMed Central