PMID- 22932816
OWN - NLM
STAT- MEDLINE
DCOM- 20130318
LR  - 20220321
IS  - 1476-5470 (Electronic)
IS  - 1466-4879 (Linking)
VI  - 13
IP  - 7
DP  - 2012 Oct
TI  - A strategy for combining minor genetic susceptibility genes to improve prediction 
      of disease in type 1 diabetes.
PG  - 549-55
LID - 10.1038/gene.2012.36 [doi]
AB  - 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.
FAU - Winkler, C
AU  - Winkler C
AD  - Institute of Diabetes Research, Helmholtz Zentrum Munchen and Forschergruppe 
      Diabetes, Klinikum rechts der Isar, Technische Universitat, Munchen, Germany.
FAU - Krumsiek, J
AU  - Krumsiek J
FAU - Lempainen, J
AU  - Lempainen J
FAU - Achenbach, P
AU  - Achenbach P
FAU - Grallert, H
AU  - Grallert H
FAU - Giannopoulou, E
AU  - Giannopoulou E
FAU - Bunk, M
AU  - Bunk M
FAU - Theis, F J
AU  - Theis FJ
FAU - Bonifacio, E
AU  - Bonifacio E
FAU - Ziegler, A-G
AU  - Ziegler AG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120830
PL  - England
TA  - Genes Immun
JT  - Genes and immunity
JID - 100953417
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Adolescent
MH  - Child
MH  - Child, Preschool
MH  - Diabetes Mellitus, Type 1/*genetics
MH  - Gene Frequency
MH  - Genetic Loci
MH  - *Genetic Predisposition to Disease
MH  - HLA Antigens/genetics
MH  - Humans
MH  - Infant
MH  - Polymorphism, Single Nucleotide
MH  - Prospective Studies
MH  - Young Adult
EDAT- 2012/08/31 06:00
MHDA- 2013/03/19 06:00
CRDT- 2012/08/31 06:00
PHST- 2012/08/31 06:00 [entrez]
PHST- 2012/08/31 06:00 [pubmed]
PHST- 2013/03/19 06:00 [medline]
AID - gene201236 [pii]
AID - 10.1038/gene.2012.36 [doi]
PST - ppublish
SO  - Genes Immun. 2012 Oct;13(7):549-55. doi: 10.1038/gene.2012.36. Epub 2012 Aug 30.