Genome-Wide Association Study of the Modified Stumvoll Insulin Sensitivity Index Identifies BCL2 and FAM19A2 as Novel Insulin Sensitivity Loci

Autor: Richard A. Jensen, Denis Rybin, Jaakko Tuomilehto, Reedik Mägi, Inga Prokopenko, Jeffrey R. O'Connell, Marcus E. Kleber, Han Chen, Geoffrey A. Walford, Allan Linnenberg, Anke Tönjes, Francis S. Collins, Sonsoles Morcillo, Gemma Rojo-Martínez, Kenneth Rice, Jose C. Florez, Leif Groop, Manuel Serrano-Ríos, Josée Dupuis, Alisa K. Manning, Peter Kovacs, Torben Jørgensen, Graciela E. Delgado, Alena Stančáková, Hans-Ulrich Häring, Claudia Langenberg, Joshua P. Lewis, Norbert Stefan, Markku Laakso, Torben Hansen, Bruce M. Psaty, Jian'an Luan, Michael Stumvoll, Mark O. Goodarzi, Robert A. Scott, Oluf Pedersen, Ching-Ti Liu, Michael N. Weedon, Michael Boehnke, Ulf Smith, David S. Siscovick, Aaron Leong, Weijia Xie, James B. Meigs, Claes Landenvall, Anne U. Jackson, Joseph M. Zmuda, Mary L. Biggs, Jerome I. Rotter, Federico Soriguer, Winfried März, Zhongyang Zhang, May E. Montasser, Arturo Corbatón-Anchuelo, J M Gómez-Zumaquero, Günther Silbernagel, Kristine Færch, Karen L. Mohlke, Heikki A. Koistinen, Yii-Der Ida Chen, Jaeyoung Hong, Gracia María Martín-Núñez, María Teresa Martínez-Larrad, Emil V. R. Appel, Niels Grarup, Harald Staiger, Johanna Kuusisto, Lars Lind, Nicholas J. Wareham, Andreas Fritsche, Stefan Gustafsson, Andrew P. Morris, Richard N. Bergman, Mark Walker, Cecilia M. Lindgren, Erik Ingelsson, Jorge R. Kizer, Timothy M. Frayling, Fausto Machicao
Rok vydání: 2023
Předmět:
Zdroj: Diabetes
Walford, G A, Gustafsson, S, Rybin, D, Stančáková, A, Chen, H, Liu, C-T, Hong, J, Jensen, R A, Rice, K, Morris, A P, Mägi, R, Tönjes, A, Prokopenko, I, Kleber, M E, Delgado, G, Silbernagel, G, Jackson, A U, Appel, E V, Grarup, N, Lewis, J P, Montasser, M E, Landenvall, C, Staiger, H, Luan, J, Frayling, T M, Weedon, M N, Xie, W, Morcillo, S, Martínez-Larrad, M T, Biggs, M L, Ida Chen, Y-D, Corbaton-Anchuelo, A, Færch, K, Zumaquero, J M, Goodarzi, M O, Kizer, J, Koistinen, H A, Leong, A, Lind, L, Lindgren, C, Machicao, F, Manning, A K, Martín-Núñez, G M, Rojo-Martínez, G, Rotter, J I, Siscovick, D S, Zmuda, J M, Zhang, Z, Serrano-Rios, M, Smith, U, Soriguer, F, Hansen, T, Jørgensen, T J, Linnenberg, A, Pedersen, O, Walker, M, Langenberg, C, Scott, R A, Wareham, N J, Fritsche, A, Häring, H-U, Stefan, N, Groop, L, O'Connell, J R, Boehnke, M, Bergman, R N, Collins, F S, Mohlke, K L, Tuomilehto, J, März, W, Kovacs, P, Stumvoll, M, Psaty, B M, Kuusisto, J, Laakso, M, Meigs, J B, Dupuis, J, Ingelsson, E & Florez, J C 2016, ' Genome-wide association study of the modified Stumvoll Insulin Sensitivity Index identifies BCL2 and FAM19A2 as novel insulin sensitivity loci ', Diabetes, vol. 65, no. 10, pp. 3200-3211 . https://doi.org/10.2337/db16-0199
DIABETES
DOI: 10.17863/cam.21298
Popis: 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.
Databáze: OpenAIRE
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