Genome-Wide Association Study of the Modified Stumvoll Insulin Sensitivity Index Identifies BCL2 and FAM19A2 as Novel Insulin Sensitivity Loci
Creators: name: Grarup, Niels
name: Morcillo, Sonsoles
name: Wareham, Nicholas J.
name: Jensen, Richard A.
name: Linnenberg, Allan
name: Dupuis, Josée
name: Laakso, Markku
name: Montasser, May E.
name: O'Connell, Jeff R.
name: Jackson, Anne U.
name: Staiger, Harald
name: Morris, Andrew P.
name: Meigs, James B.
name: Martínez-Larrad, María Teresa
name: Zhang, Zhongyang
name: Scott, Robert A.
name: Walker, Mark
name: Smith, Ulf
name: Stancáková, Alena
name: Soriguer, Federico
name: Prokopenko, Inga
name: Gustafsson, Stefan
name: Kovacs, Peter
name: Rojo-Martínez, Gemma
name: Goodarzi, Mark O.
name: Groop, Leif
name: Stefan, Norbert
name: Rice, Ken
name: Delgado, Graciela
name: Psaty, Bruce M.
name: Machicao, Fausto
name: Langenberg, Claudia
name: Rotter, Jerome I.
name: Tuomilehto, Jaakko
name: Hansen, Torben
name: Leong, Aaron
name: Lindgren, Cecilia
name: Biggs, Mary L.
name: Ingelsson, Erik
name: Kuusisto, Johanna
name: JØrgensen, Torben J.
name: Serrano-Rios, Manuel
name: Häring, Hans-Ulrich
name: Mohlke, Karen L.
name: Kleber, Marcus E.
name: Hong, Jaeyoung
name: Collins, Francis S.
name: Florez, Jose C.
name: Chen, Han
name: Appel, Emil V.
name: Corbaton-Anchuelo, Arturo
name: Luan, Jian'An
name: Manning, Alisa K.
name: Lewis, Joshua P.
name: Mägi, Reedik
name: Koistinen, Heikki A.
name: Weedon, Michael N.
name: Zmuda, Joseph M.
name: Rybin, Denis
name: Bergman, Richard N.
name: Landenvall, Claes
name: Xie, Weijia
name: Pedersen, Oluf
name: Stumvoll, Michael
name: März, Winfried
name: Fritsche, Andreas
name: Lind, Lars
name: Walford, Geoffrey A.
name: Tönjes, Anke
name: Gómez-Zumaquero, Juan Miguel
name: Martín-Núñez, Gracia María
name: Boehnke, Michael
name: Færch, Kristine
name: Silbernagel, Günther
name: Liu, Ching-Ti
name: Chen, Yii-Der Ida
name: Siscovick, David S.
name: Frayling, Timothy M.
name: Kizer, Jorge R.
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2016

description: 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.