Novel meta-analysis-derived type 2 diabetes risk loci do not determine prediabetic phenotypes.

PloS One
Harald StaigerHans-Ulrich Häring

Abstract

Genome-wide association (GWA) studies identified a series of novel type 2 diabetes risk loci. Most of them were subsequently demonstrated to affect insulin secretion of pancreatic beta-cells. Very recently, a meta-analysis of GWA data revealed nine additional risk loci with still undefined roles in the pathogenesis of type 2 diabetes. Using our thoroughly phenotyped cohort of subjects at an increased risk for type 2 diabetes, we assessed the association of the nine latest genetic variants with the predominant prediabetes traits, i.e., obesity, impaired insulin secretion, and insulin resistance. One thousand five hundred and seventy-eight metabolically characterized non-diabetic German subjects were genotyped for the reported candidate single nucleotide polymorphisms (SNPs) JAZF1 rs864745, CDC123/CAMK1D rs12779790, TSPAN8/LGR5 rs7961581, THADA rs7578597, ADAMTS9 rs4607103, NOTCH2 rs10923931, DCD rs1153188, VEGFA rs9472138, and BCL11A rs10490072. Insulin sensitivity was derived from fasting glucose and insulin concentrations, oral glucose tolerance test (OGTT), and hyperinsulinemic-euglycemic clamp. Insulin secretion was estimated from OGTT data. After appropriate adjustment for confounding variables and Bonferroni correction for...Continue Reading

References

Sep 22, 2006·Human Molecular Genetics·H Freeman, R D Cox
Apr 28, 2007·Science·UNKNOWN Diabetes Genetics Initiative of Broad Institute of Harvard and MIT, Lund University, and Novartis Institutes of BioMedical RShaun Purcell
Nov 1, 2007·The Journal of Clinical Endocrinology and Metabolism·Yasushi FurukawaKishio Nanjo
Jan 31, 2008·European Journal of Human Genetics : EJHG·Jana V van Vliet-OstaptchoukCisca Wijmenga

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Citations

Apr 29, 2014·Reproductive Biomedicine Online·Izhar Ben-Shlomo, Johnny S Younis
Oct 5, 2010·Current Diabetes Reports·Niels GrarupTorben Hansen
Dec 15, 2010·International Journal of Epidemiology·Tiago V PereiraJosé E Krieger
Feb 11, 2009·Clinical Chemistry and Laboratory Medicine : CCLM·Rob N M Weijers
Aug 25, 2010·International Journal of Obesity : Journal of the International Association for the Study of Obesity·M-F ChampyD Blom
Sep 1, 2011·Diabetes Research and Clinical Practice·Silke A SchäferKonstantinos Kantartzis
Oct 28, 2019·Bioscience Reports·Jiawei YinFengyuan Che

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Methods Mentioned

BETA
genotyping

Software Mentioned

power
JMP

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