No interactions between previously associated 2-hour glucose gene variants and physical activity or BMI on 2-hour glucose levels

Robert A Scott; Audrey Y Chu; Niels Grarup; Alisa K Manning; Marie-France Hivert; Dmitry Shungin; Anke Tönjes; Ajay Yesupriya; Daniel Barnes; Nabila Bouatia-Naji; Nicole L Glazer; Anne U Jackson; Zoltán Kutalik; Vasiliki Lagou; Diana Marek; Laura J Rasmussen-Torvik; Heather M Stringham; Toshiko Tanaka; Mette Aadahl; Dan E Arking; Sven Bergmann; Eric Boerwinkle; Lori L Bonnycastle; Stefan R Bornstein; Eric Brunner; Suzannah J Bumpstead; Soren Brage; Olga D Carlson; Han Chen; Yii-Der Ida Chen; Peter S Chines; Francis S Collins; David J Couper; Elaine M Dennison; Nicole F Dowling; Josephine S Egan; Ulf Ekelund; Michael R Erdos; Nita G Forouhi; Caroline S Fox; Mark O Goodarzi; Jürgen Grässler; Stefan Gustafsson; Göran Hallmans; Torben Hansen; Aroon Hingorani; John W Holloway; Frank B Hu; Bo Isomaa; Karen A Jameson; Ingegerd Johansson; Anna Elisabet Jonsson; Torben Jørgensen; Mika Kivimaki; Peter Kovacs; Meena Kumari; Johanna Kuusisto; Markku Laakso; Cécile Lecoeur; Claire Lévy-Marchal; Guo Li; Ruth J F Loos; Valeri Lyssenko; Michael Marmot; Pedro Marques-Vidal; Mario A Morken; Gabriele Müller; Kari E North; James S Pankow; Felicity Payne; Inga Prokopenko; Bruce M Psaty; Frida Renström; Ken Rice; Jerome I Rotter; Denis Rybin; Camilla H Sandholt; Avan A Sayer; Peter Shrader; Peter E H Schwarz; David S Siscovick; Alena Stancáková; Michael Stumvoll; Tanya M Teslovich; Gérard Waeber; Gordon H Williams; Daniel R Witte; Andrew R Wood; Weijia Xie; Michael Boehnke; Cyrus Cooper; Luigi Ferrucci; Philippe Froguel; Leif Groop; W H Linda Kao; Peter Vollenweider; Mark Walker; Richard M Watanabe; Oluf Pedersen; James B Meigs; Erik Ingelsson; Inês Barroso; Jose C Florez; Paul W Franks; Josée Dupuis; Nicholas J Wareham; Claudia Langenberg

doi:10.2337/db11-0973

No interactions between previously associated 2-hour glucose gene variants and physical activity or BMI on 2-hour glucose levels

Robert A Scott, Audrey Y Chu, Niels Grarup, Alisa K Manning, Marie-France Hivert, Dmitry Shungin, Anke Tönjes, Ajay Yesupriya, Daniel Barnes, Nabila Bouatia-Naji, Nicole L Glazer, Anne U Jackson, Zoltán Kutalik, Vasiliki Lagou, Diana Marek, Laura J Rasmussen-Torvik, Heather M Stringham, Toshiko Tanaka, Mette Aadahl, Dan E ArkingSven Bergmann, Eric Boerwinkle, Lori L Bonnycastle, Stefan R Bornstein, Eric Brunner, Suzannah J Bumpstead, Soren Brage, Olga D Carlson, Han Chen, Yii-Der Ida Chen, Peter S Chines, Francis S Collins, David J Couper, Elaine M Dennison, Nicole F Dowling, Josephine S Egan, Ulf Ekelund, Michael R Erdos, Nita G Forouhi, Caroline S Fox, Mark O Goodarzi, Jürgen Grässler, Stefan Gustafsson, Göran Hallmans, Torben Hansen, Aroon Hingorani, John W Holloway, Frank B Hu, Bo Isomaa, Karen A Jameson, Ingegerd Johansson, Anna Elisabet Jonsson, Torben Jørgensen, Mika Kivimaki, Peter Kovacs, Meena Kumari, Johanna Kuusisto, Markku Laakso, Cécile Lecoeur, Claire Lévy-Marchal, Guo Li, Ruth J F Loos, Valeri Lyssenko, Michael Marmot, Pedro Marques-Vidal, Mario A Morken, Gabriele Müller, Kari E North, James S Pankow, Felicity Payne, Inga Prokopenko, Bruce M Psaty, Frida Renström, Ken Rice, Jerome I Rotter, Denis Rybin, Camilla H Sandholt, Avan A Sayer, Peter Shrader, Peter E H Schwarz, David S Siscovick, Alena Stancáková, Michael Stumvoll, Tanya M Teslovich, Gérard Waeber, Gordon H Williams, Daniel R Witte, Andrew R Wood, Weijia Xie, Michael Boehnke, Cyrus Cooper, Luigi Ferrucci, Philippe Froguel, Leif Groop, W H Linda Kao, Peter Vollenweider, Mark Walker, Richard M Watanabe, Oluf Pedersen, James B Meigs, Erik Ingelsson, Inês Barroso, Jose C Florez, Paul W Franks, Josée Dupuis, Nicholas J Wareham, Claudia Langenberg

19 Citations (Scopus)

Abstract

Gene-lifestyle interactions have been suggested to contribute to the development of type 2 diabetes. Glucose levels 2 h after a standard 75-g glucose challenge are used to diagnose diabetes and are associated with both genetic and lifestyle factors. However, whether these factors interact to determine 2-h glucose levels is unknown. We meta-analyzed single nucleotide polymorphism (SNP) X BMI and SNP X physical activity (PA) interaction regression models for five SNPs previously associated with 2-h glucose levels from up to 22 studies comprising 54,884 individuals without diabetes. PA levels were dichotomized, with individuals below the first quintile classified as inactive (20%) and the remainder as active (80%). BMI was considered a continuous trait. Inactive individuals had higher 2-h glucose levels than active individuals (β = 0.22 mmol/L [95% CI 0.13-0.31], P = 1.63 × 10 ^-6). All SNPs were associated with 2-h glucose (β = 0.06-0.12 mmol/allele, P ≤ 1.53 × 10 ^-7), but no significant interactions were found with PA (P > 0.18) or BMI (P ≥0.04). In this large study of gene-lifestyle interaction, we observed no interactions between genetic and lifestyle factors, both of which were associated with 2-h glucose. It is perhaps unlikely that top loci from genome-wide association studies will exhibit strong subgroup-specific effects, and may not, therefore, make the best candidates for the study of interactions.

Original language	English
Journal	Diabetes
Volume	61
Issue number	5
Pages (from-to)	1291-6
Number of pages	6
ISSN	0046-0192
DOIs	https://doi.org/10.2337/db11-0973
Publication status	Published - May 2012

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Scott, R. A., Chu, A. Y., Grarup, N., Manning, A. K., Hivert, M-F., Shungin, D., Tönjes, A., Yesupriya, A., Barnes, D., Bouatia-Naji, N., Glazer, N. L., Jackson, A. U., Kutalik, Z., Lagou, V., Marek, D., Rasmussen-Torvik, L. J., Stringham, H. M., Tanaka, T., Aadahl, M., ... Langenberg, C. (2012). No interactions between previously associated 2-hour glucose gene variants and physical activity or BMI on 2-hour glucose levels. Diabetes, 61(5), 1291-6. https://doi.org/10.2337/db11-0973

Scott, RA, Chu, AY, Grarup, N, Manning, AK, Hivert, M-F, Shungin, D, Tönjes, A, Yesupriya, A, Barnes, D, Bouatia-Naji, N, Glazer, NL, Jackson, AU, Kutalik, Z, Lagou, V, Marek, D, Rasmussen-Torvik, LJ, Stringham, HM, Tanaka, T, Aadahl, M, Arking, DE, Bergmann, S, Boerwinkle, E, Bonnycastle, LL, Bornstein, SR, Brunner, E, Bumpstead, SJ, Brage, S, Carlson, OD, Chen, H, Chen, Y-DI, Chines, PS, Collins, FS, Couper, DJ, Dennison, EM, Dowling, NF, Egan, JS, Ekelund, U, Erdos, MR, Forouhi, NG, Fox, CS, Goodarzi, MO, Grässler, J, Gustafsson, S, Hallmans, G, Hansen, T, Hingorani, A, Holloway, JW, Hu, FB, Isomaa, B, Jameson, KA, Johansson, I, Jonsson, AE, Jørgensen, T, Kivimaki, M, Kovacs, P, Kumari, M, Kuusisto, J, Laakso, M, Lecoeur, C, Lévy-Marchal, C, Li, G, Loos, RJF, Lyssenko, V, Marmot, M, Marques-Vidal, P, Morken, MA, Müller, G, North, KE, Pankow, JS, Payne, F, Prokopenko, I, Psaty, BM, Renström, F, Rice, K, Rotter, JI, Rybin, D, Sandholt, CH, Sayer, AA, Shrader, P, Schwarz, PEH, Siscovick, DS, Stancáková, A, Stumvoll, M, Teslovich, TM, Waeber, G, Williams, GH, Witte, DR, Wood, AR, Xie, W, Boehnke, M, Cooper, C, Ferrucci, L, Froguel, P, Groop, L, Kao, WHL, Vollenweider, P, Walker, M, Watanabe, RM, Pedersen, O, Meigs, JB, Ingelsson, E, Barroso, I, Florez, JC, Franks, PW, Dupuis, J, Wareham, NJ & Langenberg, C 2012, 'No interactions between previously associated 2-hour glucose gene variants and physical activity or BMI on 2-hour glucose levels', Diabetes, vol. 61, no. 5, pp. 1291-6. https://doi.org/10.2337/db11-0973

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title = "No interactions between previously associated 2-hour glucose gene variants and physical activity or BMI on 2-hour glucose levels",

abstract = "Gene-lifestyle interactions have been suggested to contribute to the development of type 2 diabetes. Glucose levels 2 h after a standard 75-g glucose challenge are used to diagnose diabetes and are associated with both genetic and lifestyle factors. However, whether these factors interact to determine 2-h glucose levels is unknown. We meta-analyzed single nucleotide polymorphism (SNP) X BMI and SNP X physical activity (PA) interaction regression models for five SNPs previously associated with 2-h glucose levels from up to 22 studies comprising 54,884 individuals without diabetes. PA levels were dichotomized, with individuals below the first quintile classified as inactive (20%) and the remainder as active (80%). BMI was considered a continuous trait. Inactive individuals had higher 2-h glucose levels than active individuals (β = 0.22 mmol/L [95% CI 0.13-0.31], P = 1.63 × 10 -6). All SNPs were associated with 2-h glucose (β = 0.06-0.12 mmol/allele, P ≤ 1.53 × 10 -7), but no significant interactions were found with PA (P > 0.18) or BMI (P ≥0.04). In this large study of gene-lifestyle interaction, we observed no interactions between genetic and lifestyle factors, both of which were associated with 2-h glucose. It is perhaps unlikely that top loci from genome-wide association studies will exhibit strong subgroup-specific effects, and may not, therefore, make the best candidates for the study of interactions.",

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year = "2012",

month = may,

doi = "10.2337/db11-0973",

language = "English",

volume = "61",

pages = "1291--6",

journal = "Diabetes",

issn = "0012-1797",

publisher = "American Diabetes Association",

number = "5",

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TY - JOUR

T1 - No interactions between previously associated 2-hour glucose gene variants and physical activity or BMI on 2-hour glucose levels

AU - Scott, Robert A

AU - Chu, Audrey Y

AU - Grarup, Niels

AU - Manning, Alisa K

AU - Hivert, Marie-France

AU - Shungin, Dmitry

AU - Tönjes, Anke

AU - Yesupriya, Ajay

AU - Barnes, Daniel

AU - Bouatia-Naji, Nabila

AU - Glazer, Nicole L

AU - Jackson, Anne U

AU - Kutalik, Zoltán

AU - Lagou, Vasiliki

AU - Marek, Diana

AU - Rasmussen-Torvik, Laura J

AU - Stringham, Heather M

AU - Tanaka, Toshiko

AU - Aadahl, Mette

AU - Arking, Dan E

AU - Bergmann, Sven

AU - Boerwinkle, Eric

AU - Bonnycastle, Lori L

AU - Bornstein, Stefan R

AU - Brunner, Eric

AU - Bumpstead, Suzannah J

AU - Brage, Soren

AU - Carlson, Olga D

AU - Chen, Han

AU - Chen, Yii-Der Ida

AU - Chines, Peter S

AU - Collins, Francis S

AU - Couper, David J

AU - Dennison, Elaine M

AU - Dowling, Nicole F

AU - Egan, Josephine S

AU - Ekelund, Ulf

AU - Erdos, Michael R

AU - Forouhi, Nita G

AU - Fox, Caroline S

AU - Goodarzi, Mark O

AU - Grässler, Jürgen

AU - Gustafsson, Stefan

AU - Hallmans, Göran

AU - Hansen, Torben

AU - Hingorani, Aroon

AU - Holloway, John W

AU - Hu, Frank B

AU - Isomaa, Bo

AU - Jameson, Karen A

AU - Johansson, Ingegerd

AU - Jonsson, Anna Elisabet

AU - Jørgensen, Torben

AU - Kivimaki, Mika

AU - Kovacs, Peter

AU - Kumari, Meena

AU - Kuusisto, Johanna

AU - Laakso, Markku

AU - Lecoeur, Cécile

AU - Lévy-Marchal, Claire

AU - Li, Guo

AU - Loos, Ruth J F

AU - Lyssenko, Valeri

AU - Marmot, Michael

AU - Marques-Vidal, Pedro

AU - Morken, Mario A

AU - Müller, Gabriele

AU - North, Kari E

AU - Pankow, James S

AU - Payne, Felicity

AU - Prokopenko, Inga

AU - Psaty, Bruce M

AU - Renström, Frida

AU - Rice, Ken

AU - Rotter, Jerome I

AU - Rybin, Denis

AU - Sandholt, Camilla H

AU - Sayer, Avan A

AU - Shrader, Peter

AU - Schwarz, Peter E H

AU - Siscovick, David S

AU - Stancáková, Alena

AU - Stumvoll, Michael

AU - Teslovich, Tanya M

AU - Waeber, Gérard

AU - Williams, Gordon H

AU - Witte, Daniel R

AU - Wood, Andrew R

AU - Xie, Weijia

AU - Boehnke, Michael

AU - Cooper, Cyrus

AU - Ferrucci, Luigi

AU - Froguel, Philippe

AU - Groop, Leif

AU - Kao, W H Linda

AU - Vollenweider, Peter

AU - Walker, Mark

AU - Watanabe, Richard M

AU - Pedersen, Oluf

AU - Meigs, James B

AU - Ingelsson, Erik

AU - Barroso, Inês

AU - Florez, Jose C

AU - Franks, Paul W

AU - Dupuis, Josée

AU - Wareham, Nicholas J

AU - Langenberg, Claudia

PY - 2012/5

Y1 - 2012/5

N2 - Gene-lifestyle interactions have been suggested to contribute to the development of type 2 diabetes. Glucose levels 2 h after a standard 75-g glucose challenge are used to diagnose diabetes and are associated with both genetic and lifestyle factors. However, whether these factors interact to determine 2-h glucose levels is unknown. We meta-analyzed single nucleotide polymorphism (SNP) X BMI and SNP X physical activity (PA) interaction regression models for five SNPs previously associated with 2-h glucose levels from up to 22 studies comprising 54,884 individuals without diabetes. PA levels were dichotomized, with individuals below the first quintile classified as inactive (20%) and the remainder as active (80%). BMI was considered a continuous trait. Inactive individuals had higher 2-h glucose levels than active individuals (β = 0.22 mmol/L [95% CI 0.13-0.31], P = 1.63 × 10 -6). All SNPs were associated with 2-h glucose (β = 0.06-0.12 mmol/allele, P ≤ 1.53 × 10 -7), but no significant interactions were found with PA (P > 0.18) or BMI (P ≥0.04). In this large study of gene-lifestyle interaction, we observed no interactions between genetic and lifestyle factors, both of which were associated with 2-h glucose. It is perhaps unlikely that top loci from genome-wide association studies will exhibit strong subgroup-specific effects, and may not, therefore, make the best candidates for the study of interactions.

AB - Gene-lifestyle interactions have been suggested to contribute to the development of type 2 diabetes. Glucose levels 2 h after a standard 75-g glucose challenge are used to diagnose diabetes and are associated with both genetic and lifestyle factors. However, whether these factors interact to determine 2-h glucose levels is unknown. We meta-analyzed single nucleotide polymorphism (SNP) X BMI and SNP X physical activity (PA) interaction regression models for five SNPs previously associated with 2-h glucose levels from up to 22 studies comprising 54,884 individuals without diabetes. PA levels were dichotomized, with individuals below the first quintile classified as inactive (20%) and the remainder as active (80%). BMI was considered a continuous trait. Inactive individuals had higher 2-h glucose levels than active individuals (β = 0.22 mmol/L [95% CI 0.13-0.31], P = 1.63 × 10 -6). All SNPs were associated with 2-h glucose (β = 0.06-0.12 mmol/allele, P ≤ 1.53 × 10 -7), but no significant interactions were found with PA (P > 0.18) or BMI (P ≥0.04). In this large study of gene-lifestyle interaction, we observed no interactions between genetic and lifestyle factors, both of which were associated with 2-h glucose. It is perhaps unlikely that top loci from genome-wide association studies will exhibit strong subgroup-specific effects, and may not, therefore, make the best candidates for the study of interactions.

U2 - 10.2337/db11-0973

DO - 10.2337/db11-0973

M3 - Journal article

C2 - 22415877

SN - 0012-1797

VL - 61

SP - 1291

EP - 1296

JO - Diabetes

JF - Diabetes

IS - 5

ER -

No interactions between previously associated 2-hour glucose gene variants and physical activity or BMI on 2-hour glucose levels

Abstract

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