DESCRIPTION:

List of positional candidate genes after correcting for multiple testing and controlling the false discovery rate from genome wide association studies (GWAS) retrieved from the NHGRI-EBI Catalog of published genome-wide association studies (http://www.ebi.ac.uk/gwas/). The disease/trait examined in this study, as reported by the authors, was Glucose homeostasis traits. The EFO term glucose homeostasis measurement, glucose effectiveness measurement was annotated to this set after curation by NHGRI-EBI. Intergenic SNPS were mapped to both the upstream and downstream gene. P-value uploaded. This gene set was generated using gwas2gs v. 0.1.8 and the GWAS Catalog v. 1.0.1.

LABEL:

GWAS: glucose homeostasis measurement, glucose effectiveness measurement

SCORE TYPE:

P-Value

DATE ADDED:

2017-05-02

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

ND Palmer, MO Goodarzi, CD Langefeld, N Wang, X Guo, KD Taylor, TE Fingerlin, JM Norris, TA Buchanan, AH Xiang, T Haritunians, JT Ziegler, AH Williams, D Stefanovski, J Cui, AW Mackay, LF Henkin, RN Bergman, X Gao, J Gauderman, R Varma, CL Hanis, NJ Cox, HM Highland, JE Below, AL Williams, NP Burtt, CA Aguilar-Salinas, A Huerta-Chagoya, C Gonzalez-Villalpando, L Orozco, CA Haiman, MY Tsai, WC Johnson, J Yao, L Rasmussen-Torvik, J Pankow, B Snively, RD Jackson, S Liu, JL Nadler, F Kandeel, YD Chen, DW Bowden, SS Rich, LJ Raffel, JI Rotter, RM Watanabe, LE Wagenknecht

TITLE:

Genetic Variants Associated With Quantitative Glucose Homeostasis Traits Translate to Type 2 Diabetes in Mexican Americans: The GUARDIAN (Genetics Underlying Diabetes in Hispanics) Consortium.

JOURNAL:

Diabetes May 2015, Vol 64, pp. 1853-66

ABSTRACT:

Insulin sensitivity, insulin secretion, insulin clearance, and glucose effectiveness exhibit strong genetic components, although few studies have examined their genetic architecture or influence on type 2 diabetes (T2D) risk. We hypothesized that loci affecting variation in these quantitative traits influence T2D. We completed a multicohort genome-wide association study to search for loci influencing T2D-related quantitative traits in 4,176 Mexican Americans. Quantitative traits were measured by the frequently sampled intravenous glucose tolerance test (four cohorts) or euglycemic clamp (three cohorts), and random-effects models were used to test the association between loci and quantitative traits, adjusting for age, sex, and admixture proportions (Discovery). Analysis revealed a significant (P < 5.00 × 10(-8)) association at 11q14.3 (MTNR1B) with acute insulin response. Loci with P < 0.0001 among the quantitative traits were examined for translation to T2D risk in 6,463 T2D case and 9,232 control subjects of Mexican ancestry (Translation). Nonparametric meta-analysis of the Discovery and Translation cohorts identified significant associations at 6p24 (SLC35B3/TFAP2A) with glucose effectiveness/T2D, 11p15 (KCNQ1) with disposition index/T2D, and 6p22 (CDKAL1) and 11q14 (MTNR1B) with acute insulin response/T2D. These results suggest that T2D and insulin secretion and sensitivity have both shared and distinct genetic factors, potentially delineating genomic components of these quantitative traits that drive the risk for T2D. PUBMED: 25524916
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