Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Current Diabetes Reports
Published in: Current Diabetes Reports 12/2017

01-12-2017 | Pathogenesis of Type 1 Diabetes (A Pugliese, Section Editor)

Genetic Risk Scores for Type 1 Diabetes Prediction and Diagnosis

Authors: Maria J. Redondo, Richard A. Oram, Andrea K. Steck

Published in: Current Diabetes Reports | Issue 12/2017

Login to get access

Abstract

Purpose of Review

About 50% of the heritability of type 1 diabetes (T1D) is attributed to human leukocyte antigen (HLA) alleles and the remainder to several (close to 50) non-HLA loci. A current challenge in the field of the genetics of T1D is to apply the knowledge accumulated in the last 40 years towards differential diagnosis and risk assessment.

Recent Findings

T1D genetic risk scores seek to combine the information from HLA and non-HLA alleles to improve the accuracy of diagnosis, prediction, and prognosis. Here, we describe genetic risk scores that have been developed and validated in various settings and populations.

Summary

Several genetic scores have been proposed that merge disease risk information from multiple genetic factors to optimize the use of genetic information and ultimately improve prediction and diagnosis of T1D.
Literature
1.
Patterson CC, Dahlquist GG, Gyurus E, Green A, Soltesz G, Group ES. Incidence trends for childhood type 1 diabetes in Europe during 1989-2003 and predicted new cases 2005-20: a multicentre prospective registration study. Lancet. 2009;373(9680):2027–33.PubMedCrossRef
2.
Tao B, Pietropaolo M, Atkinson M, Schatz D, Taylor D. Estimating the cost of type 1 diabetes in the U.S.: a propensity score matching method. PLoS One. 2010;5(7):e11501.PubMedPubMedCentralCrossRef
3.
4.
5.
Noble JA, Valdes AM, Cook M, Klitz W, Thomson G, Erlich HA. The role of HLA class II genes in insulin-dependent diabetes mellitus: molecular analysis of 180 Caucasian, multiplex families. Am J Hum Genet. 1996;59(5):1134–48.PubMedPubMedCentral
6.
Parkes M, Cortes A, van Heel DA, Brown MA. Genetic insights into common pathways and complex relationships among immune-mediated diseases. Nat Rev Genet. 2013;14(9):661–73.PubMedCrossRef
7.
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(4):381–6.PubMedPubMedCentralCrossRef
8.
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. Nat Genet. 2009;41(6):703–7.PubMedPubMedCentralCrossRef
9.
Rich SS, Akolkar B, Concannon P, Erlich H, Hilner JE, Julier C, et al. Overview of the type I diabetes genetics consortium. Genes Immun. 2009;10 Suppl 1:S1–4.PubMedCrossRef
10.
11.
Vehik K, Ajami NJ, Hadley D, Petrosino JF, Burkhardt BR. The changing landscape of type 1 diabetes: recent developments and future frontiers. Curr Diabetes Rep. 2013;13(5):642–50.CrossRef
12.
Atkinson MA, Eisenbarth GS. Type 1 diabetes: new perspectives on disease pathogenesis and treatment. Lancet. 2001;358(9277):221–9.PubMedCrossRef
13.
Eisenbarth GS, Type I. diabetes mellitus. A chronic autoimmune disease. N Engl J Med. 1986;314(21):1360–8.PubMedCrossRef
14.
Insel RA, Dunne JL, Atkinson MA, Chiang JL, Dabelea D, Gottlieb PA, et al. Staging presymptomatic type 1 diabetes: a scientific statement of JDRF, the Endocrine Society, and the American Diabetes Association. Diabetes Care. 2015;38(10):1964–74.PubMedPubMedCentralCrossRef
15.
Vardi P, Dibella EE, Pasquarello TJ, Srikanta S. Islet cell autoantibodies: pathobiology and clinical applications. Diabetes Care. 1987;10(5):645–56.PubMedCrossRef
16.
Ferrara CT, Geyer SM, Liu YF, Evans-Molina C, Libman IM, Besser R, et al. Excess BMI in childhood: a modifiable risk factor for type 1 diabetes development. Diabetes Care. 2017;40:698–701.PubMedCrossRef
17.
Wherrett DK, Chiang JL, Delamater AM, DiMeglio LA, Gitelman SE, Gottlieb PA, et al. Defining pathways for development of disease-modifying therapies in children with type 1 diabetes: a consensus report. Diabetes Care. 2015;38(10):1975–85.PubMedPubMedCentralCrossRef
18.
Skyler JS, Bakris GL, Bonifacio E, Darsow T, Eckel RH, Groop L, et al. Differentiation of diabetes by pathophysiology, natural history, and prognosis. Diabetes. 2017;66(2):241–55.PubMedCrossRef
19.
Redondo MJ, Eisenbarth GS. Genetic control of autoimmunity in type I diabetes and associated disorders. Diabetologia. 2002;45(5):605–22.PubMedCrossRef
20.
Jacobsen LM, Sosenko JM, Evans-Molina C, DiMgelio L, Goland RS, Wilson DM, Atkinsion MA, Aye, T, Russell W, Wentowroth J, Geyer S, Boulware D. The risk of progression to type 1 diabetes in individuals of diverse ages with multiple autoantibodies. 249-OR. Oral presentation at the American Diabetes Association Scientific Sessions, San Diego, California. 2017.
21.
Davis AK, DuBose SN, Haller MJ, Miller KM, DiMeglio LA, Bethin KE, et al. Prevalence of detectable C-peptide according to age at diagnosis and duration of type 1 diabetes. Diabetes Care. 2015;38(3):476–81.PubMedCrossRef
22.
Hao W, Gitelman S, DiMeglio LA, Boulware D, Greenbaum CJ, Type 1 Diabetes TrialNet Study Group. Fall in C-peptide during first 4 years from diagnosis of type 1 diabetes: variable relation to age, HbA1c, and insulin dose. Diabetes Care. 2016;39(10):1664–70.PubMedPubMedCentralCrossRef
23.
Mrena S, Virtanen SM, Laippala P, Kulmala P, Hannila ML, Akerblom HK, et al. Models for predicting type 1 diabetes in siblings of affected children. Diabetes Care. 2006;29(3):662–7.PubMedCrossRef
24.
Dorman JS, Steenkiste AR, O'Leary LA, McCarthy BJ, Lorenzen T, Foley TP. Type 1 diabetes in offspring of parents with type 1 diabetes: the tip of an autoimmune iceberg? Pediatr Diabetes. 2000;1(1):17–22.PubMedCrossRef
25.
Redondo MJ, Jeffrey J, Fain PR, Eisenbarth GS, Orban T. Concordance for islet autoimmunity among monozygotic twins. N Engl J Med. 2008;359(26):2849–50.PubMedCrossRef
26.
Redondo MJ, Rewers M, Yu L, Garg S, Pilcher CC, Elliott RB, et al. Genetic determination of islet cell autoimmunity in monozygotic twin, dizygotic twin, and non-twin siblings of patients with type 1 diabetes: prospective twin study. BMJ. 1999;318(7185):698–702.PubMedPubMedCentralCrossRef
27.
Redondo MJ, Yu L, Hawa M, Mackenzie T, Pyke DA, Eisenbarth GS, et al. Heterogeneity of type I diabetes: analysis of monozygotic twins in Great Britain and the United States. Diabetologia. 2001;44(3):354–62.PubMedCrossRef
28.
29.
Johnson MB, Hattersley AT, Flanagan SE. Monogenic autoimmune diseases of the endocrine system. Lancet Diabetes Endocrinol. 2016;4(10):862–72.PubMedCrossRef
30.
31.
32.
Noble JA, Valdes AM. Genetics of the HLA region in the prediction of type 1 diabetes. Curr Diabetes Rep. 2011;11(6):533–42.CrossRef
33.
Steck AK, Armstrong TK, Babu SR, Eisenbarth GS, Type 1 Diabetes Genetics Consortium. Stepwise or linear decrease in penetrance of type 1 diabetes with lower-risk HLA genotypes over the past 40 years. Diabetes. 2011;60(3):1045–9.PubMedPubMedCentralCrossRef
34.
Erlich HA, Griffith RL, Bugawan TL, Ziegler R, Alper C, Eisenbarth G. Implication of specific DQB1 alleles in genetic susceptibility and resistance by identification of IDDM siblings with novel HLA-DQB1 allele and unusual DR2 and DR1 haplotypes. Diabetes. 1991;40(4):478–81.PubMedCrossRef
35.
Redondo MJ, Kawasaki E, Mulgrew CL, Noble JA, Erlich HA, Freed BM, et al. DR- and DQ-associated protection from type 1A diabetes: comparison of DRB1*1401 and DQA1*0102-DQB1*0602*. J Clin Endocrinol Metab. 2000;85(10):3793–7.PubMed
36.
Erlich H, Valdes AM, Noble J, Carlson JA, Varney M, Concannon P, et al. HLA DR-DQ haplotypes and genotypes and type 1 diabetes risk: analysis of the type 1 diabetes genetics consortium families. Diabetes. 2008;57(4):1084–92.PubMedPubMedCentralCrossRef
37.
Floyel T, Kaur S, Pociot F. Genes affecting beta-cell function in type 1 diabetes. Curr Diabetes Rep. 2015;15(11):97.CrossRef
38.
Groop L, Pociot F. Genetics of diabetes—are we missing the genes or the disease? Mol Cell Endocrinol. 2014;382(1):726–39.PubMedCrossRef
39.
Vafiadis P, Bennett ST, Todd JA, Nadeau J, Grabs R, Goodyer CG, et al. Insulin expression in human thymus is modulated by INS VNTR alleles at the IDDM2 locus. Nat Genet. 1997;15(3):289–92.PubMedCrossRef
40.
Pugliese A, Zeller M, Fernandez A Jr, Zalcberg LJ, Bartlett RJ, Ricordi C, et al. The insulin gene is transcribed in the human thymus and transcription levels correlated with allelic variation at the INS VNTR-IDDM2 susceptibility locus for type 1 diabetes. Nat Genet. 1997;15(3):293–7.PubMedCrossRef
41.
Onengut-Gumuscu S, Ewens KG, Spielman RS, Concannon PA. Functional polymorphism (1858C/T) in the PTPN22 gene is linked and associated with type I diabetes in multiplex families. Genes Immun. 2004;5(8):678–80.PubMedCrossRef
42.
Nistico L, Buzzetti R, Pritchard LE, Van der Auwera B, Giovannini C, Bosi E, et al. The CTLA-4 gene region of chromosome 2q33 is linked to, and associated with, type 1 diabetes. Belgian diabetes registry. Hum Mol Genet. 1996;5(7):1075–80.PubMedCrossRef
43.
de Jong VM, Zaldumbide A, van der Slik AR, Laban S, Koeleman BP, Roep BO. Variation in the CTLA4 3'UTR has phenotypic consequences for autoreactive T cells and associates with genetic risk for type 1 diabetes. Genes Immun. 2016;17(1):75–8.PubMedCrossRef
44.
Smyth DJ, Cooper JD, Bailey R, Field S, Burren O, Smink LJ, et al. A genome-wide association study of nonsynonymous SNPs identifies a type 1 diabetes locus in the interferon-induced helicase (IFIH1) region. Nat Genet. 2006;38(6):617–9.PubMedCrossRef
45.
Vella A, Cooper JD, Lowe CE, Walker N, Nutland S, Widmer B, et al. Localization of a type 1 diabetes locus in the IL2RA/CD25 region by use of tag single-nucleotide polymorphisms. Am J Hum Genet. 2005;76(5):773–9.PubMedPubMedCentralCrossRef
46.
Guo D, Li M, Zhang Y, Yang P, Eckenrode S, Hopkins D, et al. A functional variant of SUMO4, a new I kappa B alpha modifier, is associated with type 1 diabetes. Nat Genet. 2004;36(8):837–41.PubMedCrossRef
47.
Todd JA, Walker NM, Cooper JD, Smyth DJ, Downes K, Plagnol V, et al. Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes. Nat Genet. 2007;39(7):857–64.PubMedPubMedCentralCrossRef
48.
Cooper JD, Smyth DJ, Smiles AM, Plagnol V, Walker NM, Allen JE, et al. Meta-analysis of genome-wide association study data identifies additional type 1 diabetes risk loci. Nat Genet. 2008;40(12):1399–401.PubMedPubMedCentralCrossRef
49.
Steck AK, Zhang W, Bugawan TL, Barriga KJ, Blair A, Erlich HA, et al. Do non-HLA genes influence development of persistent islet autoimmunity and type 1 diabetes in children with high-risk HLA-DR,DQ genotypes? Diabetes. 2009;58(4):1028–33.PubMedPubMedCentralCrossRef
50.
•• Steck AK, Dong F, Wong R, Fouts A, Liu E, Romanos J, et al. Improving prediction of type 1 diabetes by testing non-HLA genetic variants in addition to HLA markers. Pediatr Diabetes. 2014;15(5):355–62. This was one of the first studies to demonstrate that the combination of HLA and non-HLA genes improved T1D risk prediction in children from the general population participating in the DAISY study. PubMedCrossRef
51.
Torn C, Hadley D, Lee HS, Hagopian W, Lernmark A, Simell O, et al. Role of type 1 diabetes-associated SNPs on risk of autoantibody positivity in the TEDDY study. Diabetes. 2015;64(5):1818–29.PubMedCrossRef
52.
Redondo MJ, Babu S, Zeidler A, Orban T, Yu L, Greenbaum C, et al. Specific human leukocyte antigen DQ influence on expression of antiislet autoantibodies and progression to type 1 diabetes. J Clin Endocrinol Metab. 2006;91(5):1705–13.PubMedCrossRef
53.
Lee JC, Biasci D, Roberts R, Gearry RB, Mansfield JC, Ahmad T, et al. Genome-wide association study identifies distinct genetic contributions to prognosis and susceptibility in Crohn's disease. Nat Genet. 2017;49(2):262–8.PubMedCrossRef
54.
Black MH, Lawrence JM, Pihoker C, Dolan LM, Anderson A, Rodriguez B, et al. HLA-associated phenotypes in youth with autoimmune diabetes. Pediatr Diabetes. 2013;14(2):121–8.PubMedCrossRef
55.
Cruickshanks KJ, Jobim LF, Lawler-Heavner J, Neville TG, Gay EC, Chase HP, et al. Ethnic differences in human leukocyte antigen markers of susceptibility to IDDM. Diabetes Care. 1994;17(2):132–7.PubMedCrossRef
56.
Emery LM, Babu S, Bugawan TL, Norris JM, Erlich HA, Eisenbarth GS, et al. Newborn HLA-DR,DQ genotype screening: age- and ethnicity-specific type 1 diabetes risk estimates. Pediatr Diabetes. 2005;6(3):136–44.PubMedPubMedCentralCrossRef
57.
Erlich HA, Zeidler A, Chang J, Shaw S, Raffel LJ, Klitz W, et al. HLA class II alleles and susceptibility and resistance to insulin dependent diabetes mellitus in Mexican-American families. Nat Genet. 1993;3(4):358–64.PubMedCrossRef
58.
Lipton RB, Drum M, Greeley SA, Danielson KK, Bell GI, Hagopian WA. HLA-DQ haplotypes differ by ethnicity in patients with childhood-onset diabetes. Pediatr Diabetes. 2011;12(4 Pt 2):388–95.PubMedPubMedCentralCrossRef
59.
Black MH, Dabelea D. Genetics: new HLA variants could predict T1DM risk in African Americans. Nat Rev Endocrinol. 2013;9(10):570–1.PubMedCrossRef
60.
Howson JM, Roy MS, Zeitels L, Stevens H, Todd JA. HLA class II gene associations in African American type 1 diabetes reveal a protective HLA-DRB1*03 haplotype. Diabet Med J Br Diabet Assoc. 2013;30(6):710–6.CrossRef
61.
McCarthy BJ, Lipton R, Nichol L. HLA-DQA1 and -DQB1 alleles in Latino and African American children with diabetes mellitus. J Pediatr Endocrinol Metab. 2004;17(3):297–306.PubMedCrossRef
62.
Baisch JM, Weeks T, Giles R, Hoover M, Stastny P, Capra JD. Analysis of HLA-DQ genotypes and susceptibility in insulin-dependent diabetes mellitus. N Engl J Med. 1990;322(26):1836–41.PubMedCrossRef
63.
Mayer-Davis EJ, Lawrence JM, Dabelea D, Divers J, Isom S, Dolan L, et al. Incidence trends of type 1 and type 2 diabetes among youths, 2002-2012. N Engl J Med. 2017;376(15):1419–29.PubMedPubMedCentralCrossRef
64.
Florez JC. Found in translation: a type 1 diabetes genetic risk score applied to clinical diagnosis. Diabetes Care. 2016;39(3):330–2.PubMedCrossRef
65.
Skyler JS. Primary and secondary prevention of type 1 diabetes. Diabet Med J Br Diabet Assoc. 2013;30(2):161–9.CrossRef
66.
Skyler JS, Greenbaum CJ, Lachin JM, Leschek E, Rafkin-Mervis L, Savage P, et al. Type 1 diabetes TrialNet—an international collaborative clinical trials network. Ann N Y Acad Sci. 2008;1150:14–24.PubMedPubMedCentralCrossRef
67.
Ziegler AG, Hummel M, Schenker M, Bonifacio E. Autoantibody appearance and risk for development of childhood diabetes in offspring of parents with type 1 diabetes: the 2-year analysis of the German BABYDIAB study. Diabetes. 1999;48(3):460–8.PubMedCrossRef
68.
Group TS. The environmental determinants of diabetes in the young (TEDDY) study: study design. Pediatr Diabetes. 2007;8(5):286–98.CrossRef
69.
Rewers M, Bugawan TL, Norris JM, Blair A, Beaty B, Hoffman M, et al. Newborn screening for HLA markers associated with IDDM: diabetes autoimmunity study in the young (DAISY). Diabetologia. 1996;39(7):807–12.PubMedCrossRef
70.
71.
American Diabetes Association. 2. Classification and diagnosis of diabetes. Diabetes Care. 2017;40(Suppl 1):S11–24.CrossRef
72.
Hannon TS, Arslanian SA. The changing face of diabetes in youth: lessons learned from studies of type 2 diabetes. Ann N Y Acad Sci. 2015;1353:113–37.PubMedCrossRef
73.
Redondo MJ, Rodriguez LM, Escalante M, Smith EO, Balasubramanyam A, Haymond MW. Types of pediatric diabetes mellitus defined by anti-islet autoimmunity and random C-peptide at diagnosis. Pediatr Diabetes. 2013;14(5):333–40.PubMedCrossRef
74.
•• Oram RA, Patel K, Hill A, Shields B, McDonald TJ, Jones A, et al. A type 1 diabetes genetic risk score can aid discrimination between type 1 and type 2 diabetes in young adults. Diabetes Care. 2016;39(3):337–44. These authors developed a genetic score combining HLA and non-HLA SNPs weighed by OR that discriminated between T1D and T2D in the Wellcome Trust Case Control Consortium, and validated their findings in the South West England Cohort. PubMedCrossRef
75.
Patel KA, Oram RA, Flanagan SE, De Franco E, Colclough K, Shepherd M, et al. Type 1 diabetes genetic risk score: a novel tool to discriminate monogenic and type 1 diabetes. Diabetes. 2016;65(7):2094–9.PubMedPubMedCentralCrossRef
76.
SEARCH for Diabetes in Youth Study Group, Liese AD, D’Agostino RB Jr, Hamman RF, Kilgo PD, Lawrence JM, et al. The burden of diabetes mellitus among US youth: prevalence estimates from the SEARCH for Diabetes in Youth Study. Pediatrics. 2006;118(4):1510–8.CrossRef
77.
Kaminski BM, Klingensmith GJ, Beck RW, Tamborlane WV, Lee J, Hassan K, et al. Body mass index at the time of diagnosis of autoimmune type 1 diabetes in children. J Pediatr. 2013;162(4):736–40. e1 PubMedCrossRef
78.
Redondo MJ, Rodriguez LM, Escalante M, O’Brian Smith E, Balasubramanyam A, Haymond MW. Beta cell function and BMI in ethnically diverse children with newly diagnosed autoimmune type 1 diabetes. Pediatr Diabetes. 2012;13(7):564–71.PubMedCrossRef
79.
Gerard-Gonzalez A, Gitelman SE, Cheng P, Dubose SN, Miller KM, Olson BA, et al. Comparison of autoantibody-positive and autoantibody-negative pediatric participants enrolled in the T1D exchange clinic registry. J Diabetes. 2013;5(2):216–23.PubMedCrossRef
80.
Sosenko JM, Krischer JP, Palmer JP, Mahon J, Cowie C, Greenbaum CJ, et al. A risk score for type 1 diabetes derived from autoantibody-positive participants in the diabetes prevention trial-type 1. Diabetes Care. 2008;31(3):528–33.PubMedCrossRef
81.
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.PubMedPubMedCentralCrossRef
82.
Xu P, Beam CA, Cuthbertson D, Sosenko JM, Skyler JS, Krischer JP, et al. Prognostic accuracy of immunologic and metabolic markers for type 1 diabetes in a high-risk population: receiver operating characteristic analysis. Diabetes Care. 2012;35(10):1975–80.PubMedPubMedCentralCrossRef
83.
Xu P, Wu Y, Zhu Y, Dagne G, Johnson G, Cuthbertson D, et al. Prognostic performance of metabolic indexes in predicting onset of type 1 diabetes. Diabetes Care. 2010;33(12):2508–13.PubMedPubMedCentralCrossRef
84.
Siljander HT, Simell S, Hekkala A, Lahde J, Simell T, Vahasalo P, et al. Predictive characteristics of diabetes-associated autoantibodies among children with HLA-conferred disease susceptibility in the general population. Diabetes. 2009;58(12):2835–42.PubMedPubMedCentralCrossRef
85.
Steck AK, Johnson K, Barriga KJ, Miao D, Yu L, Hutton JC, et al. Age of islet autoantibody appearance and mean levels of insulin, but not GAD or IA-2 autoantibodies, predict age of diagnosis of type 1 diabetes: diabetes autoimmunity study in the young. Diabetes Care. 2011;34(6):1397–9.PubMedPubMedCentralCrossRef
86.
Steck AK, Vehik K, Bonifacio E, Lernmark A, Ziegler AG, Hagopian WA, et al. Predictors of progression from the appearance of islet autoantibodies to early childhood diabetes: the environmental determinants of diabetes in the young (TEDDY). Diabetes Care. 2015;38(5):808–13.PubMedPubMedCentralCrossRef
87.
Tuomilehto J, Lounamaa R, Tuomilehto-Wolf E, Reunanen A, Virtala E, Kaprio EA, et al. Epidemiology of childhood diabetes mellitus in Finland—background of a nationwide study of type 1 (insulin-dependent) diabetes mellitus. The Childhood Diabetes in Finland (DiMe) study group. Diabetologia. 1992;35(1):70–6.PubMedCrossRef
88.
Lin Y, Qian X, Krischer J, Vehik K, Lee HS, Huang S. A rule-based prognostic model for type 1 diabetes by identifying and synthesizing baseline profile patterns. PLoS One. 2014;9(6):e91095.PubMedPubMedCentralCrossRef
89.
90.
Watkins RA, Evans-Molina C, Blum JS, DiMeglio LA. Established and emerging biomarkers for the prediction of type 1 diabetes: a systematic review. Transl Res J Lab Clin Med. 2014;164(2):110–21.CrossRef
91.
Abraham G, Tye-Din JA, Bhalala OG, Kowalczyk A, Zobel J, Inouye M. Accurate and robust genomic prediction of celiac disease using statistical learning. PLoS Genet. 2014;10(2):e1004137.PubMedPubMedCentralCrossRef
92.
Evans DM, Visscher PM, Wray NR. Harnessing the information contained within genome-wide association studies to improve individual prediction of complex disease risk. Hum Mol Genet. 2009;18(18):3525–31.PubMedCrossRef
93.
Lee SH, Wray NR, Goddard ME, Visscher PM. Estimating missing heritability for disease from genome-wide association studies. Am J Hum Genet. 2011;88(3):294–305.PubMedPubMedCentralCrossRef
94.
Meigs JB, Shrader P, Sullivan LM, McAteer JB, Fox CS, Dupuis J, et al. Genotype score in addition to common risk factors for prediction of type 2 diabetes. N Engl J Med. 2008;359(21):2208–19.PubMedPubMedCentralCrossRef
95.
Rose G. Strategy of prevention: lessons from cardiovascular disease. Br Med J. 1981;282(6279):1847–51.CrossRef
96.
97.
Barker JM, Triolo TM, Aly TA, Baschal EE, Babu SR, Kretowski A, et al. Two single nucleotide polymorphisms identify the highest-risk diabetes HLA genotype: potential for rapid screening. Diabetes. 2008;57(11):3152–5.PubMedPubMedCentralCrossRef
98.
Nguyen C, Varney MD, Harrison LC, Morahan G. Definition of high-risk type 1 diabetes HLA-DR and HLA-DQ types using only three single nucleotide polymorphisms. Diabetes. 2013;62(6):2135–40.PubMedPubMedCentralCrossRef
99.
Abraham G, Kowalczyk A, Zobel J, Inouye M. SparSNP: fast and memory-efficient analysis of all SNPs for phenotype prediction. BMC Bioinformatics. 2012;13:88.PubMedPubMedCentralCrossRef
100.
Abraham G, Kowalczyk A, Zobel J, Inouye M. Performance and robustness of penalized and unpenalized methods for genetic prediction of complex human disease. Genet Epidemiol. 2013;37(2):184–95.PubMedCrossRef
101.
102.
103.
104.
Aly TA, Ide A, Jahromi MM, Barker JM, Fernando MS, Babu SR, et al. Extreme genetic risk for type 1A diabetes. Proc Natl Acad Sci U S A. 2006;103(38):14074–9.PubMedPubMedCentralCrossRef
105.
Winkler C, Krumsiek J, Lempainen J, Achenbach P, Grallert H, Giannopoulou E, et al. A strategy for combining minor genetic susceptibility genes to improve prediction of disease in type 1 diabetes. Genes Immun. 2012;13(7):549–55.PubMedCrossRef
106.
•• Winkler C, Krumsiek J, Buettner F, Angermuller C, Giannopoulou EZ, Theis FJ, et al. Feature ranking of type 1 diabetes susceptibility genes improves prediction of type 1 diabetes. Diabetologia. 2014;57(12):2521–9. This study demonstrated that a genetic score including HLA and non-HLA SNPs weighed based on their OR predicted T1D risk in high risk children participants in the BABYDIAB study. PubMedCrossRef
107.
Brorsson CA, Nielsen LB, Andersen ML, Kaur S, Bergholdt R, Hansen L, et al. Genetic risk score modelling for disease progression in new-onset type 1 diabetes patients: increased genetic load of islet-expressed and cytokine-regulated candidate genes predicts poorer glycemic control. J Diabetes Res. 2016;2016:9570424.PubMedPubMedCentralCrossRef
108.
Frohnert BI, Ide L, Dong F, Baron AE, Steck AK, Norris JM, et al. Late-onset islet autoimmunity in childhood: the Diabetes Autoimmunity Study in the Young (DAISY). Diabetologia. 2017;60(6):998–1006.PubMedCrossRef
109.
Gao S, Jia S, Hessner MJ, Wang X. Predicting disease-related subnetworks for type 1 diabetes using a new network activity score. Omics J Integr Biol. 2012;16(10):566–78.
110.
Metadata
Title
Genetic Risk Scores for Type 1 Diabetes Prediction and Diagnosis
Authors
Maria J. Redondo
Richard A. Oram
Andrea K. Steck
Publication date
01-12-2017
Publisher
Springer US
Published in
Current Diabetes Reports / Issue 12/2017
Print ISSN: 1534-4827
Electronic ISSN: 1539-0829
DOI
https://doi.org/10.1007/s11892-017-0961-5

Other articles of this Issue 12/2017

Current Diabetes Reports 12/2017 Go to the issue

Lifestyle Management to Reduce Diabetes/Cardiovascular Risk (B Conway and H Keenan, Section Editors)

Understanding Cultural Influences on Dietary Habits in Asian, Middle Eastern, and Latino Patients with Type 2 Diabetes: A Review of Current Literature and Future Directions

Hospital Management of Diabetes (A Wallia and JJ Seley, Section Editors)

Hypoglycemia Reduction Strategies in the ICU

Macrovascular Complications in Diabetes (VR Aroda and A Getaneh, Section Editors)

Cardiometabolic Risk in PCOS: More than a Reproductive Disorder

Microvascular Complications—Neuropathy (R Pop-Busui, Section Editor)

Cardiorespiratory Fitness and Cardiac Autonomic Function in Diabetes

Pathogenesis of Type 1 Diabetes (A Pugliese, Section Editor)

Autoimmune Responses to Exosomes and Candidate Antigens Contribute to Type 1 Diabetes in Non-Obese Diabetic Mice

Pharmacologic Treatment of Type 2 Diabetes (HE Lebovitz and G Bahtiyar, Section Editors)

Current Therapies That Modify Glucagon Secretion: What Is the Therapeutic Effect of Such Modifications?
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits