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Definition of High-Risk Type 1 Diabetes HLA-DR and HLA-DQ Types Using Only Three Single Nucleotide Polymorphisms

Evaluating risk of developing type 1 diabetes (T1D) depends on determining an individual’s HLA type, especially of the HLA DRB1 and DQB1 alleles. Individuals positive for HLA-DRB1*03 (DR3) or HLA-DRB1*04 (DR4) with DQB1*03:02 (DQ8) have the highest risk of developing T1D. Currently, HLA typing metho...

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Detalles Bibliográficos
Autores principales: Nguyen, Cao, Varney, Michael D., Harrison, Leonard C., Morahan, Grant
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3661605/
https://www.ncbi.nlm.nih.gov/pubmed/23378606
http://dx.doi.org/10.2337/db12-1398
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author Nguyen, Cao
Varney, Michael D.
Harrison, Leonard C.
Morahan, Grant
author_facet Nguyen, Cao
Varney, Michael D.
Harrison, Leonard C.
Morahan, Grant
author_sort Nguyen, Cao
collection PubMed
description Evaluating risk of developing type 1 diabetes (T1D) depends on determining an individual’s HLA type, especially of the HLA DRB1 and DQB1 alleles. Individuals positive for HLA-DRB1*03 (DR3) or HLA-DRB1*04 (DR4) with DQB1*03:02 (DQ8) have the highest risk of developing T1D. Currently, HLA typing methods are relatively expensive and time consuming. We sought to determine the minimum number of single nucleotide polymorphisms (SNPs) that could rapidly define the HLA-DR types relevant to T1D, namely, DR3/4, DR3/3, DR4/4, DR3/X, DR4/X, and DRX/X (where X is neither DR3 nor DR4), and could distinguish the highest-risk DR4 type (DR4-DQ8) as well as the non-T1D–associated DR4-DQB1*03:01 type. We analyzed 19,035 SNPs of 10,579 subjects (7,405 from a discovery set and 3,174 from a validation set) from the Type 1 Diabetes Genetics Consortium and developed a novel machine learning method to select as few as three SNPs that could define the HLA-DR and HLA-DQ types accurately. The overall accuracy was 99.3%, area under curve was 0.997, true-positive rates were >0.99, and false-positive rates were <0.001. We confirmed the reliability of these SNPs by 10-fold cross-validation. Our approach predicts HLA-DR/DQ types relevant to T1D more accurately than existing methods and is rapid and cost-effective.
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spelling pubmed-36616052014-06-01 Definition of High-Risk Type 1 Diabetes HLA-DR and HLA-DQ Types Using Only Three Single Nucleotide Polymorphisms Nguyen, Cao Varney, Michael D. Harrison, Leonard C. Morahan, Grant Diabetes Original Research Evaluating risk of developing type 1 diabetes (T1D) depends on determining an individual’s HLA type, especially of the HLA DRB1 and DQB1 alleles. Individuals positive for HLA-DRB1*03 (DR3) or HLA-DRB1*04 (DR4) with DQB1*03:02 (DQ8) have the highest risk of developing T1D. Currently, HLA typing methods are relatively expensive and time consuming. We sought to determine the minimum number of single nucleotide polymorphisms (SNPs) that could rapidly define the HLA-DR types relevant to T1D, namely, DR3/4, DR3/3, DR4/4, DR3/X, DR4/X, and DRX/X (where X is neither DR3 nor DR4), and could distinguish the highest-risk DR4 type (DR4-DQ8) as well as the non-T1D–associated DR4-DQB1*03:01 type. We analyzed 19,035 SNPs of 10,579 subjects (7,405 from a discovery set and 3,174 from a validation set) from the Type 1 Diabetes Genetics Consortium and developed a novel machine learning method to select as few as three SNPs that could define the HLA-DR and HLA-DQ types accurately. The overall accuracy was 99.3%, area under curve was 0.997, true-positive rates were >0.99, and false-positive rates were <0.001. We confirmed the reliability of these SNPs by 10-fold cross-validation. Our approach predicts HLA-DR/DQ types relevant to T1D more accurately than existing methods and is rapid and cost-effective. American Diabetes Association 2013-06 2013-05-17 /pmc/articles/PMC3661605/ /pubmed/23378606 http://dx.doi.org/10.2337/db12-1398 Text en © 2013 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
spellingShingle Original Research
Nguyen, Cao
Varney, Michael D.
Harrison, Leonard C.
Morahan, Grant
Definition of High-Risk Type 1 Diabetes HLA-DR and HLA-DQ Types Using Only Three Single Nucleotide Polymorphisms
title Definition of High-Risk Type 1 Diabetes HLA-DR and HLA-DQ Types Using Only Three Single Nucleotide Polymorphisms
title_full Definition of High-Risk Type 1 Diabetes HLA-DR and HLA-DQ Types Using Only Three Single Nucleotide Polymorphisms
title_fullStr Definition of High-Risk Type 1 Diabetes HLA-DR and HLA-DQ Types Using Only Three Single Nucleotide Polymorphisms
title_full_unstemmed Definition of High-Risk Type 1 Diabetes HLA-DR and HLA-DQ Types Using Only Three Single Nucleotide Polymorphisms
title_short Definition of High-Risk Type 1 Diabetes HLA-DR and HLA-DQ Types Using Only Three Single Nucleotide Polymorphisms
title_sort definition of high-risk type 1 diabetes hla-dr and hla-dq types using only three single nucleotide polymorphisms
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3661605/
https://www.ncbi.nlm.nih.gov/pubmed/23378606
http://dx.doi.org/10.2337/db12-1398
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