RT Journal Article
T1 Genome-Wide Association Study of the Modified Stumvoll Insulin Sensitivity Index Identifies BCL2 and FAM19A2 as Novel Insulin Sensitivity Loci.
A1 Walford, Geoffrey A
A1 Gustafsson, Stefan
A1 Rybin, Denis
A1 Stancakova, Alena
A1 Chen, Han
A1 Liu, Ching-Ti
A1 Hong, Jaeyoung
A1 Jensen, Richard A
A1 Rice, Ken
A1 Morris, Andrew P
A1 Magi, Reedik
A1 Tönjes, Anke
A1 Prokopenko, Inga
A1 Kleber, Marcus E
A1 Delgado, Graciela
A1 Silbernagel, Günther
A1 Jackson, Anne U
A1 Appel, Emil V
A1 Grarup, Niels
A1 Lewis, Joshua P
A1 Montasser, May E
A1 Landenvall, Claes
A1 Staiger, Harald
A1 Luan, Jian'an
A1 Frayling, Timothy M
A1 Weedon, Michael N
A1 Xie, Weijia
A1 Morcillo, Sonsoles
A1 Martinez-Larrad, Maria Teresa
A1 Biggs, Mary L
A1 Chen, Yii-Der Ida
A1 Corbaton-Anchuelo, Arturo
A1 Færch, Kristine
A1 Gomez-Zumaquero, Juan Miguel
A1 Goodarzi, Mark O
A1 Kizer, Jorge R
A1 Koistinen, Heikki A
A1 Leong, Aaron
A1 Lind, Lars
A1 Lindgren, Cecilia
A1 Machicao, Fausto
A1 Manning, Alisa K
A1 Martin-Nuñez, Gracia Maria
A1 Rojo-Martinez, Gemma
A1 Rotter, Jerome I
A1 Siscovick, David S
A1 Zmuda, Joseph M
A1 Zhang, Zhongyang
A1 Serrano-Rios, Manuel
A1 Smith, Ulf
A1 Soriguer, Federico
A1 Hansen, Torben
A1 Jørgensen, Torben J
A1 Linnenberg, Allan
A1 Pedersen, Oluf
A1 Walker, Mark
A1 Langenberg, Claudia
A1 Scott, Robert A
A1 Wareham, Nicholas J
A1 Fritsche, Andreas
A1 Häring, Hans-Ulrich
A1 Stefan, Norbert
A1 Groop, Leif
A1 O'Connell, Jeff R
A1 Boehnke, Michael
A1 Bergman, Richard N
A1 Collins, Francis S
A1 Mohlke, Karen L
A1 Tuomilehto, Jaakko
A1 März, Winfried
A1 Kovacs, Peter
A1 Stumvoll, Michael
A1 Psaty, Bruce M
A1 Kuusisto, Johanna
A1 Laakso, Markku
A1 Meigs, James B
A1 Dupuis, Josee
A1 Ingelsson, Erik
A1 Florez, Jose C
K1 Insulin Resistance
K1 Polymorphism, Single Nucleotide
K1 Proto-Oncogene Proteins c-bcl-2
AB 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.
PB American Diabetes Association
YR 2016
FD 2016-07-05
LK http://hdl.handle.net/10668/10268
UL http://hdl.handle.net/10668/10268
LA en
NO Walford GA, Gustafsson S, Rybin D, Stančáková A, Chen H, Liu CT, et al. Genome-Wide Association Study of the Modified Stumvoll Insulin Sensitivity Index Identifies BCL2 and FAM19A2 as Novel Insulin Sensitivity Loci. Diabetes. 2016 Oct;65(10):3200-11
DS RISalud
RD Apr 18, 2025