- Home
- Featured Publications
- Center Publications
- Type 1 Diabetes Risk in African-Ancestry Participants and Utility of an Ancestry-Specific Genetic Risk Score.
Type 1 Diabetes Risk in African-Ancestry Participants and Utility of an Ancestry-Specific Genetic Risk Score.
Citation | “Type 1 Diabetes Risk In African-Ancestry Participants And Utility Of An Ancestry-Specific Genetic Risk Score.”. Diabetes Care, pp. 406-415. . |
Center | University of Alabama at Birmingham University of Washington |
Multicenter |
Multicenter
|
Author | Suna Onengut-Gumuscu, Wei-Min Chen, Catherine C Robertson, Jessica K Bonnie, Emily Farber, Zhennan Zhu, Jorge R Oksenberg, Steven R Brant, Louis Bridges, Jeffrey C Edberg, Robert P Kimberly, Peter K Gregersen, Marian J Rewers, Andrea K Steck, Mary H Black, Dana Dabelea, Catherine Pihoker, Mark A Atkinson, Lynne E Wagenknecht, Jasmin Divers, Ronny A Bell, SEARCH for Diabetes in Youth, Type 1 Diabetes Genetics Consortium, Henry A Erlich, Patrick Concannon, Stephen S Rich |
Abstract |
OBJECTIVE: Genetic risk scores (GRS) have been developed that differentiate individuals with type 1 diabetes from those with other forms of diabetes and are starting to be used for population screening; however, most studies were conducted in European-ancestry populations. This study identifies novel genetic variants associated with type 1 diabetes risk in African-ancestry participants and develops an African-specific GRS. RESEARCH DESIGN AND METHODS: We generated single nucleotide polymorphism (SNP) data with the ImmunoChip on 1,021 African-ancestry participants with type 1 diabetes and 2,928 control participants. HLA class I and class II alleles were imputed using SNP2HLA. Logistic regression models were used to identify genome-wide significant ( < 5.0 × 10) SNPs associated with type 1 diabetes in the African-ancestry samples and validate SNPs associated with risk in known European-ancestry loci ( < 2.79 × 10). RESULTS: African-specific (HLA-*03:01-HLA-*02:01) and known European-ancestry HLA haplotypes (HLA-*03:01-HLA-*05:01-HLA-*02:01, HLA-*04:01-HLA-*03:01-HLA-*03:02) were significantly associated with type 1 diabetes risk. Among European-ancestry defined non-HLA risk loci, six risk loci were significantly associated with type 1 diabetes in subjects of African ancestry. An African-specific GRS provided strong prediction of type 1 diabetes risk (area under the curve 0.871), performing significantly better than a European-based GRS and two polygenic risk scores in independent discovery and validation cohorts. CONCLUSIONS: Genetic risk of type 1 diabetes includes ancestry-specific, disease-associated variants. The GRS developed here provides improved prediction of type 1 diabetes in African-ancestry subjects and a means to identify groups of individuals who would benefit from immune monitoring for early detection of islet autoimmunity. |
Year of Publication |
2019
|
Journal |
Diabetes care
|
Volume |
42
|
Issue |
3
|
Number of Pages |
406-415
|
Date Published |
12/2019
|
ISSN Number |
1935-5548
|
DOI |
10.2337/dc18-1727
|
Alternate Journal |
Diabetes Care
|
PMID |
30659077
|
PMCID |
PMC6385701
|
Download citation |