| Literature DB >> 27416945 |
Geoffrey A Walford1, Stefan Gustafsson2, Denis Rybin3, Alena Stančáková4, Han Chen5, Ching-Ti Liu6, Jaeyoung Hong6, Richard A Jensen7, Ken Rice8, Andrew P Morris9, Reedik Mägi10, Anke Tönjes11, Inga Prokopenko12, Marcus E Kleber13, Graciela Delgado13, Günther Silbernagel14, Anne U Jackson15, Emil V Appel16, Niels Grarup16, Joshua P Lewis17, May E Montasser17, Claes Landenvall18, Harald Staiger19, Jian'an Luan20, Timothy M Frayling21, Michael N Weedon21, Weijia Xie21, Sonsoles Morcillo22, María Teresa Martínez-Larrad23, Mary L Biggs24, Yii-Der Ida Chen25, Arturo Corbaton-Anchuelo23, Kristine Færch26, Juan Miguel Gómez-Zumaquero27, Mark O Goodarzi28, Jorge R Kizer29, Heikki A Koistinen30, Aaron Leong31, Lars Lind2, Cecilia Lindgren32, Fausto Machicao33, Alisa K Manning34, Gracia María Martín-Núñez35, Gemma Rojo-Martínez36, Jerome I Rotter25, David S Siscovick37, Joseph M Zmuda38, Zhongyang Zhang39, Manuel Serrano-Rios23, Ulf Smith40, Federico Soriguer36, Torben Hansen16, Torben J Jørgensen41, Allan Linnenberg42, Oluf Pedersen16, Mark Walker43, Claudia Langenberg20, Robert A Scott20, Nicholas J Wareham20, Andreas Fritsche19, Hans-Ulrich Häring19, Norbert Stefan19, Leif Groop44, Jeff R O'Connell17, Michael Boehnke15, Richard N Bergman45, Francis S Collins46, Karen L Mohlke47, Jaakko Tuomilehto48, Winfried März49, Peter Kovacs50, Michael Stumvoll11, Bruce M Psaty51, Johanna Kuusisto52, Markku Laakso52, James B Meigs53, Josée Dupuis54, Erik Ingelsson55, Jose C Florez56.
Abstract
Genome-wide association studies (GWAS) have found few common variants that influence fasting measures of insulin sensitivity. We hypothesized that a GWAS of an integrated assessment of fasting and dynamic measures of insulin sensitivity would detect novel common variants. We performed a GWAS of the modified Stumvoll Insulin Sensitivity Index (ISI) within the Meta-Analyses of Glucose and Insulin-Related Traits Consortium. Discovery for genetic association was performed in 16,753 individuals, and replication was attempted for the 23 most significant novel loci in 13,354 independent individuals. Association with ISI was tested in models adjusted for age, sex, and BMI and in a model analyzing the combined influence of the genotype effect adjusted for BMI and the interaction effect between the genotype and BMI on ISI (model 3). In model 3, three variants reached genome-wide significance: rs13422522 (NYAP2; P = 8.87 × 10(-11)), rs12454712 (BCL2; P = 2.7 × 10(-8)), and rs10506418 (FAM19A2; P = 1.9 × 10(-8)). The association at NYAP2 was eliminated by conditioning on the known IRS1 insulin sensitivity locus; the BCL2 and FAM19A2 associations were independent of known cardiometabolic loci. In conclusion, we identified two novel loci and replicated known variants associated with insulin sensitivity. Further studies are needed to clarify the causal variant and function at the BCL2 and FAM19A2 loci.Entities:
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Year: 2016 PMID： 27416945 PMCID： PMC5033262 DOI： 10.2337/db16-0199
Source DB: PubMed Journal: Diabetes ISSN： 0012-1797 Impact factor: 9.461