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Winkler, C. ; Krumsiek, J. ; Lempainen, J. ; Achenbach, P. ; Grallert, H. ; Giannopoulou, E.Z. ; Bunk, M. ; Theis, F.J. ; Bonifacio, E.* ; Ziegler, A.-G.

A strategy for combining minor genetic susceptibility genes to improve prediction of disease in type 1 diabetes.

Genes Immun. 13, 549-555 (2012)
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Genome-wide association studies have identified gene regions associated with type 1 diabetes. The aim of this study was to determine how the combined allele frequency of multiple susceptibility genes can stratify islet autoimmunity and/or type 1 diabetes risk. Children of parents with type 1 diabetes and prospectively followed from birth for the development of islet autoantibodies and diabetes were genotyped for single-nucleotide polymorphisms at 12 type 1 diabetes susceptibility genes (ERBB3, PTPN2, IFIH1, PTPN22, KIAA0350, CD25, CTLA4, SH2B3, IL2, IL18RAP, IL10 and COBL). Non-human leukocyte antigen (HLA) risk score was defined by the total number of risk alleles at these genes. Receiver operator curve analysis showed that the non-HLA gene combinations were highly effective in discriminating diabetes and most effective in children with a high-risk HLA genotype. The greatest diabetes discrimination was obtained by the sum of risk alleles for eight genes (IFIH1, CTLA4, PTPN22, IL18RAP, SH2B3, KIAA0350, COBL and ERBB3) in the HLA-risk children. Non-HLA-risk allele scores stratified risk for developing islet autoantibodies and diabetes, and progression from islet autoimmunity to diabetes. Genotyping at multiple susceptibility loci in children from affected families can identify neonates with sufficient genetic risk of type 1 diabetes to be considered for early intervention.
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Publication type Article: Journal article
Document type Scientific Article
Keywords type 1 diabetes; type 1 diabetes susceptibility genes; islet autoimmunity; ANTIBODY STANDARDIZATION PROGRAM; GERMAN BABYDIAB; RISK; AUTOIMMUNITY; AUTOANTIBODIES; PROGRESSION; POLYMORPHISMS; ASSOCIATION; GENOTYPES; MELLITUS
Language
Publication Year 2012
HGF-reported in Year 2012
ISSN (print) / ISBN 1466-4879
e-ISSN 1476-5470
Journal Genes and Immunity
Quellenangaben Volume: 13, Issue: 7, Pages: 549-555 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes Research (IDF)
Institute of Bioinformatics and Systems Biology (IBIS)
Research Unit Molecular Epidemiology (AME)
German Center for Diabetes Reseach (DZD)
Institute of Pancreatic Islet Research (IPI)
POF-Topic(s) 30201 - Metabolic Health
30505 - New Technologies for Biomedical Discoveries
30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
90000 - German Center for Diabetes Research
Research field(s) Helmholtz Diabetes Center
Enabling and Novel Technologies
Genetics and Epidemiology
PSP Element(s) G-502100-001
G-503700-004
G-504200-002
G-501900-421
DOI 10.1038/gene.2012.36
WOS ID WOS:000310216100006
Scopus ID 84867741377
PubMed ID 22932816
Erfassungsdatum 2012-10-31
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