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Hormone and Metabolic Research
Article . 2009 . Peer-reviewed
Data sources: Crossref
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Lack of Significant Effects of the Type 2 Diabetes Susceptibility LociJAZF1,CDC123/CAMK1D,NOTCH2,ADAMTS9,THADA, andTSPAN8/LGR5on Diabetes and Quantitative Metabolic Traits

Authors: Schleinitz, D; Tönjes, A; Böttcher, Y; Dietrich, K; Enigk, B; Koriath, M; Scholz, G; +5 Authors

Lack of Significant Effects of the Type 2 Diabetes Susceptibility LociJAZF1,CDC123/CAMK1D,NOTCH2,ADAMTS9,THADA, andTSPAN8/LGR5on Diabetes and Quantitative Metabolic Traits

Abstract

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.

Country
United Kingdom
Related Organizations
Keywords

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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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
20
Average
Average
Top 10%
Green