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- Title
Type 1 Diabetes Risk in African-Ancestry Participants and Utility of an Ancestry-Specific Genetic Risk Score.
- Authors
Onengut-Gumuscu, Suna; Wei-Min Chen; Robertson, Catherine C.; Bonnie, Jessica K.; Farber, Emily; Zhennan Zhu; Oksenberg, Jorge R.; Brant, Steven R.; Bridges Jr, S. Louis; Edberg, Jeffrey C.; Kimberly, Robert P.; Gregersen, Peter K.; Rewers, Marian J.; Steck, Andrea K.; Black, Mary H.; Dabelea, Dana; Pihoker, Catherine; Atkinson, Mark A.; Wagenknecht, Lynne E.; Divers, Jasmin
- Abstract
<bold>Objective: </bold>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.<bold>Research Design and Methods: </bold>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 (P < 5.0 × 10-8) SNPs associated with type 1 diabetes in the African-ancestry samples and validate SNPs associated with risk in known European-ancestry loci (P < 2.79 × 10-5).<bold>Results: </bold>African-specific (HLA-DQA1*03:01-HLA-DQB1*02:01) and known European-ancestry HLA haplotypes (HLA-DRB1*03:01-HLA-DQA1*05:01-HLA-DQB1*02:01, HLA-DRB1*04:01-HLA-DQA1*03:01-HLA-DQB1*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.<bold>Conclusions: </bold>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.
- Subjects
TYPE 1 diabetes; SINGLE nucleotide polymorphisms; ARTIFICIAL pancreases; LOGISTIC regression analysis; FORECASTING
- Publication
Diabetes Care, 2019, Vol 42, Issue 3, p406
- ISSN
0149-5992
- Publication type
journal article
- DOI
10.2337/dc18-1727