Type 1 Diabetes Risk in African-Ancestry Participants and Utility of an Ancestry-Specific Genetic Risk Score

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 v...

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Bibliographic Details
Published in:Diabetes care Vol. 42; no. 3; p. 406
Main Authors: Onengut-Gumuscu, Suna, Chen, Wei-Min, Robertson, Catherine C, Bonnie, Jessica K, Farber, Emily, Zhu, Zhennan, 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, Bell, Ronny A, Erlich, Henry A, Concannon, Patrick, Rich, Stephen S
Format: Journal Article
Language:English
Published: United States 01.03.2019
Subjects:
Alleles
Black People - genetics
Black People - statistics & numerical data
Case-Control Studies
Diabetes Mellitus, Type 1 - ethnology
Diabetes Mellitus, Type 1 - genetics
Female
Genetic Predisposition to Disease
Genetic Testing - methods
Genetic Testing - standards
Genome-Wide Association Study
Haplotypes
HLA-D Antigens - genetics
HLA-DQ alpha-Chains - genetics
HLA-DQ beta-Chains - genetics
HLA-DRB1 Chains - genetics
Humans
Male
Polymorphism, Single Nucleotide
Predictive Value of Tests
Research Design
Risk Factors
White People - genetics
ISSN:1935-5548, 1935-5548
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Summary: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. 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 ). 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. 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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ISSN:1935-5548
1935-5548
DOI:10.2337/dc18-1727