Type 1 Diabetes Risk in African-Ancestry Participants and Utility of an Ancestry-Specific Genetic Risk Score.
Diabetes Care
; 42(3): 406-415, 2019 03.
Article
em En
| MEDLINE
| ID: mdl-30659077
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 ANDMETHODS:
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).RESULTS:
African-specific (HLA-DQA1*0301-HLA-DQB1*0201) and known European-ancestry HLA haplotypes (HLA-DRB1*0301-HLA-DQA1*0501-HLA-DQB1*0201, HLA-DRB1*0401-HLA-DQA1*0301-HLA-DQB1*0302) 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.
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Base de dados:
MEDLINE
Assunto principal:
Antígenos HLA-D
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Testes Genéticos
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População Negra
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Diabetes Mellitus Tipo 1
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article