Dataset Information

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

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.

SUBMITTER: Palmer ND

PROVIDER: S-EPMC4407862 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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

Palmer Nicholette D ND Goodarzi Mark O MO Langefeld Carl D CD Wang Nan N Guo Xiuqing X Taylor Kent D KD Fingerlin Tasha E TE Norris Jill M JM Buchanan Thomas A TA Xiang Anny H AH Haritunians Talin T Ziegler Julie T JT Williams Adrienne H AH Stefanovski Darko D Cui Jinrui J Mackay Adrienne W AW Henkin Leora F LF Bergman Richard N RN Gao Xiaoyi X Gauderman James J Varma Rohit R Hanis Craig L CL Cox Nancy J NJ Highland Heather M HM Below Jennifer E JE Williams Amy L AL Burtt Noel P NP Aguilar-Salinas Carlos A CA Huerta-Chagoya Alicia A Gonzalez-Villalpando Clicerio C Orozco Lorena L Haiman Christopher A CA Tsai Michael Y MY Johnson W Craig WC Yao Jie J Rasmussen-Torvik Laura L Pankow James J Snively Beverly B Jackson Rebecca D RD Liu Simin S Nadler Jerry L JL Kandeel Fouad F Chen Yii-Der I YD Bowden Donald W DW Rich Stephen S SS Raffel Leslie J LJ Rotter Jerome I JI Watanabe Richard M RM Wagenknecht Lynne E LE

Diabetes 20141218 5

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 ...[more]

PMID: 25524916

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Dataset Information

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

Publications

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

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