Assessment of type 1 diabetes risk conferred by HLA-DRB1, INS-VNTR and PTPN22 genes using the Bayesian network approach.
<h4>Background</h4>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...
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| Autores principales: | , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2013
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/f45aba6aeced43929912b64771026ad6 |
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| Sumario: | <h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions/significance</h4>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. |
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