Lack of Significant Effects of the Type 2 Diabetes Susceptibility LociJAZF1,CDC123/CAMK1D,NOTCH2,ADAMTS9,THADA, andTSPAN8/LGR5on Diabetes and Quantitative Metabolic Traits
pmid: 19670153
Lack of Significant Effects of the Type 2 Diabetes Susceptibility LociJAZF1,CDC123/CAMK1D,NOTCH2,ADAMTS9,THADA, andTSPAN8/LGR5on Diabetes and Quantitative Metabolic Traits
Recently, several novel loci reaching genome-wide significance levels for type 2 diabetes (T2D) were identified through a meta-analysis of three genome-wide scans and large-scale follow-up. The aim of our study was to investigate the association of these loci with T2D and related subphenotypes in two cohorts from Germany. We performed an association study of 9 SNPs in or around JAZF1, CDC123/ CAMK1D, NOTCH2, BCL11A, ADAMTS9, VEGFA, DCD, THADA, and TSPAN8/ LGR5 with T2D and related quantitative traits (fasting insulin and glucose, indices derived from OGTT) in the isolated population of Sorbs (205 cases and 695 controls) and in a mixed German population (Leipzig) (938 subjects with and 918 without T2D). None of the variants was associated with T2D, but the meta-analysis of both cohorts revealed a modest trend of association of rs7578597 in THADA with T2D (p=0.055). Furthermore, Sorbian subjects homozygous for the rs7578597 T-allele had lower mean 30-minute plasma insulin when compared with carriers of the C-allele (p<0.05). The T-allele was also nominally associated with higher fasting plasma glucose in the Leipzig cohort (p<0.05). Although several other SNPs showed some evidence for association with T2D-related traits the effects were not replicated within our study. Associations of the T2D-risk alleles with T2D or related subphenotypes were overall very weak in the approximately 2 700 subjects studied. This is compatible with the modest effect size of these "second sweep" variants, which will require large-scale association studies on quantitative traits to clarify their role in the pathophysiology of T2D.
- University of Oxford United Kingdom
- Leipzig University Germany
Adult, Male, Membrane Glycoproteins, ADAMTS9 Protein, Cell Cycle Proteins, Cohort Studies, DNA-Binding Proteins, ADAM Proteins, Glucose, Calcium-Calmodulin-Dependent Protein Kinase Type 1, Diabetes Mellitus, Type 2, Antigens, Neoplasm, Case-Control Studies, Germany, Humans, Insulin, Female, Genetic Predisposition to Disease, Co-Repressor Proteins, Genome-Wide Association Study
Adult, Male, Membrane Glycoproteins, ADAMTS9 Protein, Cell Cycle Proteins, Cohort Studies, DNA-Binding Proteins, ADAM Proteins, Glucose, Calcium-Calmodulin-Dependent Protein Kinase Type 1, Diabetes Mellitus, Type 2, Antigens, Neoplasm, Case-Control Studies, Germany, Humans, Insulin, Female, Genetic Predisposition to Disease, Co-Repressor Proteins, Genome-Wide Association Study
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