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Title: Genome-Wide Association Study of the Modified Stumvoll Insulin Sensitivity Index Identifies BCL2 and FAM19A2 as Novel Insulin Sensitivity Loci.
Authors: Walford, Geoffrey A
Gustafsson, Stefan
Rybin, Denis
Stančáková, Alena
Chen, Han
Liu, Ching-Ti
Hong, Jaeyoung
Jensen, Richard A
Rice, Ken
Morris, Andrew P
Mägi, Reedik
Tönjes, Anke
Prokopenko, Inga
Kleber, Marcus E
Delgado, Graciela
Silbernagel, Günther
Jackson, Anne U
Appel, Emil V
Grarup, Niels
Lewis, Joshua P
Montasser, May E
Landenvall, Claes
Staiger, Harald
Luan, Jian'an
Frayling, Timothy M
Weedon, Michael N
Xie, Weijia
Morcillo, Sonsoles
Martínez-Larrad, María Teresa
Biggs, Mary L
Chen, Yii-Der Ida
Corbaton-Anchuelo, Arturo
Færch, Kristine
Gómez-Zumaquero, Juan Miguel
Goodarzi, Mark O
Kizer, Jorge R
Koistinen, Heikki A
Leong, Aaron
Lind, Lars
Lindgren, Cecilia
Machicao, Fausto
Manning, Alisa K
Martín-Núñez, Gracia María
Rojo-Martínez, Gemma
Rotter, Jerome I
Siscovick, David S
Zmuda, Joseph M
Zhang, Zhongyang
Serrano-Rios, Manuel
Smith, Ulf
Soriguer, Federico
Hansen, Torben
Jørgensen, Torben J
Linnenberg, Allan
Pedersen, Oluf
Walker, Mark
Langenberg, Claudia
Scott, Robert A
Wareham, Nicholas J
Fritsche, Andreas
Häring, Hans-Ulrich
Stefan, Norbert
Groop, Leif
O'Connell, Jeff R
Boehnke, Michael
Bergman, Richard N
Collins, Francis S
Mohlke, Karen L
Tuomilehto, Jaakko
März, Winfried
Kovacs, Peter
Stumvoll, Michael
Psaty, Bruce M
Kuusisto, Johanna
Laakso, Markku
Meigs, James B
Dupuis, Josée
Ingelsson, Erik
Florez, Jose C
metadata.dc.subject.mesh: Chemokines, CC
Genetic Predisposition to Disease
Genome-Wide Association Study
Insulin Receptor Substrate Proteins
Insulin Resistance
Polymorphism, Single Nucleotide
Proto-Oncogene Proteins c-bcl-2
Issue Date: 14-Jul-2016
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.
metadata.dc.identifier.doi: 10.2337/db16-0199
Appears in Collections:Producción 2020

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