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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.

Original publication

DOI

10.1055/s-0029-1233480

Type

Journal article

Journal

Horm Metab Res

Publication Date

01/2010

Volume

42

Pages

14 - 22

Keywords

ADAM Proteins, ADAMTS9 Protein, Adult, Antigens, Neoplasm, Calcium-Calmodulin-Dependent Protein Kinase Type 1, Case-Control Studies, Cell Cycle Proteins, Cohort Studies, Diabetes Mellitus, Type 2, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Germany, Glucose, Humans, Insulin, Male, Membrane Glycoproteins, Middle Aged, Neoplasm Proteins, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Receptor, Notch2, Receptors, G-Protein-Coupled, Tetraspanins