Diabetes (New York, N.Y.), 2014-01, Vol.63 (1), p.369-376
2014
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Details
- Autor(en) / Beteiligte
- Titel
- A genome-wide association study in American Indians implicates DNER as a susceptibility locus for type 2 diabetes
- Ist Teil von
- Diabetes (New York, N.Y.), 2014-01, Vol.63 (1), p.369-376
- Ort / Verlag
- United States: American Diabetes Association
- Erscheinungsjahr
- 2014
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Most genetic variants associated with type 2 diabetes mellitus (T2DM) have been identified through genome-wide association studies (GWASs) in Europeans. The current study reports a GWAS for young-onset T2DM in American Indians. Participants were selected from a longitudinal study conducted in Pima Indians and included 278 cases with diabetes with onset before 25 years of age, 295 nondiabetic controls ≥45 years of age, and 267 siblings of cases or controls. Individuals were genotyped on a ∼1M single nucleotide polymorphism (SNP) array, resulting in 453,654 SNPs with minor allele frequency >0.05. SNPs were analyzed for association in cases and controls, and a family-based association test was conducted. Tag SNPs (n = 311) were selected for 499 SNPs associated with diabetes (P < 0.0005 in case-control analyses or P < 0.0003 in family-based analyses), and these SNPs were genotyped in up to 6,834 additional Pima Indians to assess replication. Rs1861612 in DNER was associated with T2DM (odds ratio = 1.29 per copy of the T allele; P = 6.6 × 10(-8), which represents genome-wide significance accounting for the number of effectively independent SNPs analyzed). Transfection studies in murine pancreatic β-cells suggested that DNER regulates expression of notch signaling pathway genes. These studies implicate DNER as a susceptibility gene for T2DM in American Indians.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0012-1797eISSN: 1939-327XDOI: 10.2337/db13-0416Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3868048
- Format
- –
- Schlagworte
- Adolescent, Adult, Aged, Alleles, Analysis, Cells, Diabetes, Diabetes Mellitus, Type 2 - ethnology, Diabetes Mellitus, Type 2 - genetics, Female, Gene expression, Gene Frequency, Genetic aspects, Genetic Predisposition to Disease, Genetic susceptibility, Genetic variation, Genetics/Genomes/Proteomics/Metabolomics, Genome-Wide Association Study, Genotype, Genotype & phenotype, Humans, Identification and classification, Indians, North American - genetics, Male, Middle Aged, Native North Americans, Nerve Tissue Proteins - genetics, Polymorphism, Polymorphism, Single Nucleotide, Receptors, Cell Surface - genetics, Type 2 diabetes