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 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 Stančáková; 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 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 Stančáková, 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

School of Medicine

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

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 (US)
Pages (from-to)	1291-1296
Number of pages	6
Journal	Diabetes
Volume	61
Issue number	5
DOIs	https://doi.org/10.2337/db11-0973
State	Published - May 2012

ASJC Scopus subject areas

Internal Medicine
Endocrinology, Diabetes and Metabolism

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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), 1291-1296. https://doi.org/10.2337/db11-0973

Scott, RA, Chu, AY, Grarup, N, Manning, AK, Hivert, MF, 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, YDI, 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, A, 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, Stančáková, 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. 1291-1296. 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.",

author = "Scott, {Robert A.} and Chu, {Audrey Y.} and Niels Grarup and Manning, {Alisa K.} and Hivert, {Marie France} and Dmitry Shungin and Anke T{\"o}njes and Ajay Yesupriya and Daniel Barnes and Nabila Bouatia-Naji and Glazer, {Nicole L.} and Jackson, {Anne U.} and Zolt{\'a}n Kutalik and Vasiliki Lagou and Diana Marek and Rasmussen-Torvik, {Laura J.} and Stringham, {Heather M.} and Toshiko Tanaka and Mette Aadahl and Arking, {Dan E.} and Sven Bergmann and Eric Boerwinkle and Bonnycastle, {Lori L.} and Bornstein, {Stefan R.} and Eric Brunner and Bumpstead, {Suzannah J.} and Soren Brage and Carlson, {Olga D.} and Han Chen and Chen, {Yii Der Ida} and Chines, {Peter S.} and Collins, {Francis S.} and Couper, {David J.} and Dennison, {Elaine M.} and Dowling, {Nicole F.} and Egan, {Josephine S.} and Ulf Ekelund and Erdos, {Michael R.} and Forouhi, {Nita G.} and Fox, {Caroline S.} and Goodarzi, {Mark O.} and J{\"u}rgen Gr{\"a}ssler and Stefan Gustafsson and G{\"o}ran Hallmans and Torben Hansen and Aroon Hingorani and Holloway, {John W.} and Hu, {Frank B.} and Bo Isomaa and Jameson, {Karen A.} and Ingegerd Johansson and Anna Jonsson and Torben J{\o}rgensen and Mika Kivimaki and Peter Kovacs and Meena Kumari and Johanna Kuusisto and Markku Laakso and C{\'e}cile Lecoeur and Claire L{\'e}vy-Marchal and Guo Li and Loos, {Ruth J.F.} and Valeri Lyssenko and Michael Marmot and Pedro Marques-Vidal and Morken, {Mario A.} and Gabriele M{\"u}ller and North, {Kari E.} and Pankow, {James S.} and Felicity Payne and Inga Prokopenko and Psaty, {Bruce M.} and Frida Renstr{\"o}m and Ken Rice and Rotter, {Jerome I.} and Denis Rybin and Sandholt, {Camilla H.} and Sayer, {Avan A.} and Peter Shrader and Schwarz, {Peter E.H.} and Siscovick, {David S.} and Alena Stan{\v c}{\'a}kov{\'a} and Michael Stumvoll and Teslovich, {Tanya M.} and G{\'e}rard Waeber and Williams, {Gordon H.} and Witte, {Daniel R.} and Wood, {Andrew R.} and Weijia Xie and Michael Boehnke and Cyrus Cooper and Luigi Ferrucci and Philippe Froguel and Leif Groop and Kao, {W. H.Linda} and Peter Vollenweider and Mark Walker and Watanabe, {Richard M.} and Oluf Pedersen and Meigs, {James B.} and Erik Ingelsson and In{\^e}s Barroso and Florez, {Jose C.} and Franks, {Paul W.} and Jos{\'e}e Dupuis and Wareham, {Nicholas J.} and Claudia Langenberg",

year = "2012",

month = may,

doi = "10.2337/db11-0973",

language = "English (US)",

volume = "61",

pages = "1291--1296",

journal = "Diabetes",

issn = "0012-1797",

publisher = "American Diabetes Association Inc.",

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

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 - Stančáková, 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.

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U2 - 10.2337/db11-0973

DO - 10.2337/db11-0973

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AN - SCOPUS:84860587659

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

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