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Type 1 Diabetes Risk in African-Ancestry Participants and Utility of an Ancestry-Specific Genetic Risk Score.
Onengut-Gumuscu, Suna; Chen, Wei-Min; Robertson, Catherine C; Bonnie, Jessica K; Farber, Emily; Zhu, Zhennan; Oksenberg, Jorge R; Brant, Steven R; Bridges, 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.
Afiliação
  • Onengut-Gumuscu S; Center for Public Health Genomics, University of Virginia, Charlottesville, VA.
  • Chen WM; Department of Public Health Sciences, University of Virginia, Charlottesville, VA.
  • Robertson CC; Center for Public Health Genomics, University of Virginia, Charlottesville, VA.
  • Bonnie JK; Department of Public Health Sciences, University of Virginia, Charlottesville, VA.
  • Farber E; Center for Public Health Genomics, University of Virginia, Charlottesville, VA.
  • Zhu Z; Center for Public Health Genomics, University of Virginia, Charlottesville, VA.
  • Oksenberg JR; Center for Public Health Genomics, University of Virginia, Charlottesville, VA.
  • Brant SR; Center for Public Health Genomics, University of Virginia, Charlottesville, VA.
  • Bridges SL; Department of Neurology, School of Medicine, University of California, San Francisco, San Francisco, CA.
  • Edberg JC; Meyerhoff Inflammatory Bowel Disease Center, Department of Medicine, School of Medicine, and Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD.
  • Kimberly RP; Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL.
  • Gregersen PK; Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL.
  • Rewers MJ; Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL.
  • Steck AK; Robert S. Boas Center for Genomics & Human Genetics, The Feinstein Institute for Medical Research, Manhasset, NY.
  • Black MH; Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, CO.
  • Dabelea D; Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, CO.
  • Pihoker C; Ambry Genetics, Aliso Viejo, CA.
  • Atkinson MA; Colorado School of Public Health, University of Colorado Denver, Aurora, CO.
  • Wagenknecht LE; Department of Pediatrics, University of Washington, Seattle, WA.
  • Divers J; Diabetes Institute and Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL.
  • Bell RA; Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, NC.
  • Rich SS; Center for Genetics, Children's Hospital Oakland Research Institute, Oakland, CA.
Diabetes Care ; 42(3): 406-415, 2019 03.
Artigo em Inglês | 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 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 (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.
Assuntos
Texto completo: Disponível Coleções: Bases de dados internacionais Contexto em Saúde: ODS3 - Saúde e Bem-Estar Tema em saúde: Meta 3.4: Reduzir as mortes prematuras devido doenças não transmissíveis Base de dados: MEDLINE Assunto principal: Antígenos HLA-D / Testes Genéticos / Grupo com Ancestrais do Continente Africano / Diabetes Mellitus Tipo 1 Tipo de estudo: Estudo de rastreamento Limite: Feminino / Humanos / Masculino Idioma: Inglês Revista: Diabetes Care Ano de publicação: 2019 Tipo de documento: Artigo País de afiliação: Vaticano

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Texto completo: Disponível Coleções: Bases de dados internacionais Contexto em Saúde: ODS3 - Saúde e Bem-Estar Tema em saúde: Meta 3.4: Reduzir as mortes prematuras devido doenças não transmissíveis Base de dados: MEDLINE Assunto principal: Antígenos HLA-D / Testes Genéticos / Grupo com Ancestrais do Continente Africano / Diabetes Mellitus Tipo 1 Tipo de estudo: Estudo de rastreamento Limite: Feminino / Humanos / Masculino Idioma: Inglês Revista: Diabetes Care Ano de publicação: 2019 Tipo de documento: Artigo País de afiliação: Vaticano