Receiver Operating Characteristic Analysis of HLA, CTLA4, and Insulin Genotypes for Type 1 Diabetes
| Autor: | Michael D. Varney, Janelle A. Noble, Ana M. Valdes, Henry A. Erlich |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Genotype Endocrinology Diabetes and Metabolism 030209 endocrinology & metabolism Single-nucleotide polymorphism Human leukocyte antigen Polymorphism Single Nucleotide 03 medical and health sciences 0302 clinical medicine HLA-DQ Antigens Internal Medicine Humans Insulin SNP Medicine CTLA-4 Antigen Genetic Predisposition to Disease Allele Genotyping Alleles Original Research Aged 030304 developmental biology Advanced and Specialized Nursing Genetics 0303 health sciences Receiver operating characteristic business.industry Haplotype Clinical Care/Education/Nutrition/Psychosocial Research Middle Aged Diabetes Mellitus Type 1 Haplotypes Female business |
| Zdroj: | Diabetes Care |
| ISSN: | 1935-5548 0149-5992 |
| DOI: | 10.2337/dc12-2284 |
| Popis: | OBJECTIVE This study assessed the ability to distinguish between type 1 diabetes–affected individuals and their unaffected relatives using HLA and single nucleotide polymorphism (SNP) genotypes. RESEARCH DESIGN AND METHODS Eight models, ranging from only the high-risk DR3/DR4 genotype to all significantly associated HLA genotypes and two SNPs mapping to the cytotoxic T-cell–associated antigen-4 gene (CTLA4) and insulin (INS) genes, were fitted to high-resolution class I and class II HLA genotyping data for patients from the Type 1 Diabetes Genetics Consortium collection. Pairs of affected individuals and their unaffected siblings were divided into a “discovery” (n = 1,015 pairs) and a “validation” set (n = 318 pairs). The discriminating performance of various combinations of genetic information was estimated using receiver operating characteristic (ROC) curve analysis. RESULTS The use of only the presence or absence of the high-risk DR3/DR4 genotype achieved very modest discriminating ability, yielding an area under the curve (AUC) of 0.62 in the discovery set and 0.59 in the validation set. The full model—which included HLA information from the class II loci DPB1, DRB1, and DQB1; selected alleles from HLA class I loci A and B; and SNPs from the CTLA4 and INS genes—increased the AUC to 0.74 in the discovery set and to 0.71 in the validation set. A cost-effective alternative is proposed, using genotype information equivalent to typing four SNPs (DR3, DR4-DQB1*03:02, CTLA-4, and INS), which achieved an AUC of 0.72 in the discovery set and 0.69 in the validation set. CONCLUSIONS Genotyping data sufficient to tag DR3, DR4-DQB1*03:02, CTLA4, and INS were shown to distinguish between subjects with type 1 diabetes and their unaffected siblings adequately to achieve clinically utility to identify children in multiplex families to be considered for early intervention. |
| Databáze: | OpenAIRE |
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