A genome-wide association study in American Indians implicates DNER as a susceptibility locus for type 2 diabetes
| Autor: | Leslie J. Baier, Ke Huang, V. Ossowski, Li Bian, Jeff Sutherland, Maryam Abdussamad, Christopher Wiedrich, Robert L. Hanson, Yunhua L. Muller, E. Jennifer Weil, Clifton Bogardus, Darin Mahkee, Tingwei Guo, Sayuko Kobes, Robert G. Nelson, Michael Traurig, Peter H. Bennett, Kim Wiedrich, William C. Knowler |
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| Rok vydání: | 2013 |
| Předmět: |
Adult
Male endocrine system diseases Adolescent Genotype Endocrinology Diabetes and Metabolism 030209 endocrinology & metabolism Genome-wide association study Single-nucleotide polymorphism Nerve Tissue Proteins Receptors Cell Surface Biology Polymorphism Single Nucleotide 03 medical and health sciences 0302 clinical medicine Gene Frequency Polymorphism (computer science) Internal Medicine SNP Humans Genetic Predisposition to Disease Allele Allele frequency Alleles 030304 developmental biology Genetic association Aged Genetics 0303 health sciences Genetics/Genomes/Proteomics/Metabolomics Middle Aged Minor allele frequency Diabetes Mellitus Type 2 Indians North American Female Genome-Wide Association Study |
| Zdroj: | Diabetes |
| ISSN: | 1939-327X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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