title: Assessment of type 1 diabetes risk conferred by HLA-DRB1, INS-VNTR and PTPN22 genes using the Bayesian network approach.
abstract: BACKGROUND
  Determining genetic risk is a fundamental prerequisite for the implementation of primary prevention trials for type 1 diabetes (T1D). The aim of this study was to assess the risk conferred by HLA-DRB1, INS-VNTR and PTPN22 single genes on the onset of T1D and the joint risk conferred by all these three susceptibility loci using the Bayesian Network (BN) approach in both population-based case-control and family clustering data sets.
  
  
  RESULTS
  A case-control French cohort, consisting of 868 T1D patients and 73 French control subjects, a French family data set consisting of 1694 T1D patients and 2340 controls were analysed. We studied both samples separately applying the BN probabilistic approach, that is a graphical model that encodes probabilistic relationships among variables of interest. As expected HLA-DRB1 is the most relevant susceptibility gene. We proved that INS and PTPN22 genes marginally influence T1D risk in all risk HLA-DRB1 genotype categories. The absolute risk conferred by carrying simultaneously high, moderate or low risk HLA-DRB1 genotypes together with at risk INS and PTPN22 genotypes, was 11.5%, 1.7% and 0.1% in the case-control sample and 19.8%, 6.6% and 2.2% in the family cohort, respectively.
  
  
  CONCLUSIONS
  This work represents, to the best of our knowledge, the first study based on both case-control and family data sets, showing the joint effect of HLA, INS and PTPN22 in a T1D Caucasian population with a wide range of age at T1D onset, adding new insights to previous findings regarding data sets consisting of patients and controls <15 years at onset.
authors.affiliation: Department of Endocrinology and Diabetes, University Campus Bio-Medico, Rome, Italy ; Department of Gynecology, University Campus Bio-Medico, Rome, Italy.
authors.forename: Rosalba
authors.initials: R
authors.lastname: Portuesi
authors.forename: Paolo
authors.initials: P
authors.lastname: Pozzilli
authors.forename: Bernhard
authors.initials: B
authors.lastname: Boehm
authors.forename: Raffaella
authors.initials: R
authors.lastname: Buzzetti
authors.forename: Simonetta
authors.initials: S
authors.lastname: Filippi
mesh_terms: D000293:Adolescent; D000328:Adult; D001499:Bayes Theorem; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006801:Humans; D007328:Insulin / Q000235:genetics; D008297:Male; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics*; D055815:Young Adult
chemical_list: D059811:HLA-DRB1 Chains; D007328:Insulin; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22