Genome-wide physical activity interactions in adiposity ― A meta-analysis of 200,452 adults

Mariaelisa Graff, Robert A. Scott, Anne E. Justice, Kristin L. Young, Mary F. Feitosa, Llilda Barata, Thomas W. Winkler, Audrey Y. Chu, Anubha Mahajan, David Hadley, Luting Xue, Tsegaselassie Workalemahu, Nancy L. Heard-Costa, Marcel den Hoed, Tarunveer S. Ahluwalia, Qibin Qi, Julius S. Ngwa, Frida Renström, Lydia Quaye, John D. Eicher & 233 others James E. Hayes, Marilyn Cornelis, Zoltan Kutalik, Elise Lim, Jian’an Luan, Jennifer E. Huffman, Weihua Zhang, Wei Zhao, Paula J. Griffin, Toomas Haller, Shafqat Ahmad, Pedro M. Marques-Vidal, Stephanie Bien, Loic Yengo, Alexander Teumer, Albert Vernon Smith, Meena Kumari, Marie Neergaard Harder, Johanne Marie Justesen, Marcus E. Kleber, Mette Hollensted, Kurt Lohman, Natalia V. Rivera, John B. Whitfield, Jing Hua Zhao, Heather M. Stringham, Leo Pekka Lyytikäinen, Charlotte Huppertz, Gonneke Willemsen, Wouter J. Peyrot, Ying Wu, Kati Kristiansson, Ayse Demirkan, Myriam Fornage, Maija Hassinen, Lawrence F. Bielak, Gemma Cadby, Toshiko Tanaka, Reedik Mägi, Peter J. Van Der Most, Anne U. Jackson, Jennifer L. Bragg-Gresham, Veronique Vitart, Jonathan Marten, Pau Navarro, Claire Bellis, Dorota Pasko, Åsa Johansson, Søren Snitker, Ching Yu Cheng, Joel Eriksson, Unhee Lim, Mette Aadahl, Linda S. Adair, Najaf Amin, Beverley Balkau, Juha Auvinen, John Beilby, Richard N. Bergman, Sven Bergmann, Alain G. Bertoni, John Blangero, Amélie Bonnefond, Lori L. Bonnycastle, Judith B. Borja, Søren Brage, Fabio Busonero, Steve Buyske, Harry Campbell, Peter S. Chines, Francis S. Collins, Tanguy Corre, George Davey Smith, Graciela E. Delgado, Nicole Dueker, Marcus Dörr, Tapani Ebeling, Gudny Eiriksdottir, Tõnu Esko, Jessica D. Faul, Mao Fu, Kristine Færch, Christian Gieger, Sven Gläser, Jian Gong, Penny Gordon-Larsen, Harald Grallert, Tanja B. Grammer, Niels Grarup, Gerard van Grootheest, Kennet Harald, Nicholas D. Hastie, Aki S. Havulinna, Dena G. Hernandez, Lucia Hindorff, Lynne J. Hocking, Oddgeir L. Holmens, Christina Holzapfel, Jouke Jan Hottenga, Jie Huang, Tao Huang, Jennie Hui, Cornelia Huth, Nina Hutri-Kähönen, Alan L. James, John Olov Jansson, Min A. Jhun, Markus Juonala, Leena Kinnunen, Heikki A. Koistinen, Ivana Kolcic, Pirjo Komulainen, Johanna Kuusisto, Kirsti Kvaløy, Mika Kähönen, Timo A. Lakka, Lenore J. Launer, Benjamin Lehne, Cecilia M. Lindgren, Mattias Lorentzon, Robert N Luben, Michel Marre, Yuri Milaneschi, Keri L. Monda, Grant W. Montgomery, Marleen H.M. De Moor, Antonella Mulas, Martina Müller-Nurasyid, A. W. Musk, Reija Männikkö, Satu Männistö, Narisu Narisu, Matthias Nauck, Jennifer A. Nettleton, Ilja M. Nolte, Albertine J. Oldehinkel, Matthias Olden, Ken K. Ong, Sandosh Padmanabhan, Lavinia Paternoster, Jeremiah Perez, Markus Perola, Annette Peters, Ulrike Peters, Patricia A. Peyser, Inga Prokopenko, Hannu Puolijoki, Olli T. Raitakari, Tuomo Rankinen, Laura J. Rasmussen-Torvik, Rajesh Rawal, Paul M. Ridker, Lynda M. Rose, Igor Rudan, Cinzia Sarti, Mark A. Sarzynski, Kai Savonen, William R. Scott, Serena Sanna, Alan R. Shuldiner, Steve Sidney, Günther Silbernagel, Blair H. Smith, Jennifer A. Smith, Harold Snieder, Alena Stančáková, Barbara Sternfeld, Amy J. Swift, Tuija Tammelin, Sian Tsung Tan, Barbara Thorand, Dorothée Thuillier, Liesbeth Vandenput, Henrik Vestergaard, Jana V. Van Vliet-Ostaptchouk, Marie Claude Vohl, Uwe Völker, Gérard Waeber, Mark Walker, Sarah H. Wild, Andrew Wong, Alan F. Wright, M. Carola Zillikens, Niha Zubair, Christopher A. Haiman, Loic Lemarchand, Ulf Gyllensten, Claes Ohlsson, Albert Hofman, Fernando Rivadeneira, André G. Uitterlinden, Louis Pérusse, James F. Wilson, Caroline Hayward, Ozren Polasek, Francesco Cucca, Kristian Hveem, Catharina A. Hartman, Anke Tönjes, Stefania Bandinelli, Lyle J. Palmer, Sharon L R Kardia, Rainer Rauramaa, Thorkild I A Sørensen, Jaakko Tuomilehto, Veikko Salomaa, Brenda W J H Penninx, Eco J C N De Geus, Dorret I. Boomsma, Terho Lehtimäki, Massimo Mangino, Markku Laakso, Claude Bouchard, Nicholas G. Martin, Diana Kuh, Yongmei Liu, Allan Linneberg, Winfried März, Konstantin Strauch, Mika Kivimäki, Tamara B. Harris, Vilmundur Gudnason, Henry Völzke, Lu Qi, Marjo Riitta Järvelin, John C. Chambers, Jaspal S. Kooner, Philippe Froguel, Charles Kooperberg, Peter Vollenweider, CHARGE consortium, EPIC-InterAct Consortium, PAGE Consortium

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Abstract

Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by ~30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.

LanguageEnglish
Article numbere1006528
JournalPLoS Genetics
Volume13
Issue number4
DOIs
StatePublished - 1 Apr 2017

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physical activity
Adiposity
meta-analysis
adiposity
Meta-Analysis
genome
Genome
Obesity
Waist-Hip Ratio
Genetic Association Studies
Waist Circumference
loci
obesity
Genes
waist
gene
waist circumference
hips
ancestry
environmental factor

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Graff, M., Scott, R. A., Justice, A. E., Young, K. L., Feitosa, M. F., Barata, L., ... PAGE Consortium (2017). Genome-wide physical activity interactions in adiposity ― A meta-analysis of 200,452 adults. PLoS Genetics, 13(4), [e1006528]. DOI: 10.1371/journal.pgen.1006528
Graff, Mariaelisa ; Scott, Robert A. ; Justice, Anne E. ; Young, Kristin L. ; Feitosa, Mary F. ; Barata, Llilda ; Winkler, Thomas W. ; Chu, Audrey Y. ; Mahajan, Anubha ; Hadley, David ; Xue, Luting ; Workalemahu, Tsegaselassie ; Heard-Costa, Nancy L. ; den Hoed, Marcel ; Ahluwalia, Tarunveer S. ; Qi, Qibin ; Ngwa, Julius S. ; Renström, Frida ; Quaye, Lydia ; Eicher, John D. ; Hayes, James E. ; Cornelis, Marilyn ; Kutalik, Zoltan ; Lim, Elise ; Luan, Jian’an ; Huffman, Jennifer E. ; Zhang, Weihua ; Zhao, Wei ; Griffin, Paula J. ; Haller, Toomas ; Ahmad, Shafqat ; Marques-Vidal, Pedro M. ; Bien, Stephanie ; Yengo, Loic ; Teumer, Alexander ; Smith, Albert Vernon ; Kumari, Meena ; Harder, Marie Neergaard ; Justesen, Johanne Marie ; Kleber, Marcus E. ; Hollensted, Mette ; Lohman, Kurt ; Rivera, Natalia V. ; Whitfield, John B. ; Zhao, Jing Hua ; Stringham, Heather M. ; Lyytikäinen, Leo Pekka ; Huppertz, Charlotte ; Willemsen, Gonneke ; Peyrot, Wouter J. ; Wu, Ying ; Kristiansson, Kati ; Demirkan, Ayse ; Fornage, Myriam ; Hassinen, Maija ; Bielak, Lawrence F. ; Cadby, Gemma ; Tanaka, Toshiko ; Mägi, Reedik ; Van Der Most, Peter J. ; Jackson, Anne U. ; Bragg-Gresham, Jennifer L. ; Vitart, Veronique ; Marten, Jonathan ; Navarro, Pau ; Bellis, Claire ; Pasko, Dorota ; Johansson, Åsa ; Snitker, Søren ; Cheng, Ching Yu ; Eriksson, Joel ; Lim, Unhee ; Aadahl, Mette ; Adair, Linda S. ; Amin, Najaf ; Balkau, Beverley ; Auvinen, Juha ; Beilby, John ; Bergman, Richard N. ; Bergmann, Sven ; Bertoni, Alain G. ; Blangero, John ; Bonnefond, Amélie ; Bonnycastle, Lori L. ; Borja, Judith B. ; Brage, Søren ; Busonero, Fabio ; Buyske, Steve ; Campbell, Harry ; Chines, Peter S. ; Collins, Francis S. ; Corre, Tanguy ; Smith, George Davey ; Delgado, Graciela E. ; Dueker, Nicole ; Dörr, Marcus ; Ebeling, Tapani ; Eiriksdottir, Gudny ; Esko, Tõnu ; Faul, Jessica D. ; Fu, Mao ; Færch, Kristine ; Gieger, Christian ; Gläser, Sven ; Gong, Jian ; Gordon-Larsen, Penny ; Grallert, Harald ; Grammer, Tanja B. ; Grarup, Niels ; van Grootheest, Gerard ; Harald, Kennet ; Hastie, Nicholas D. ; Havulinna, Aki S. ; Hernandez, Dena G. ; Hindorff, Lucia ; Hocking, Lynne J. ; Holmens, Oddgeir L. ; Holzapfel, Christina ; Hottenga, Jouke Jan ; Huang, Jie ; Huang, Tao ; Hui, Jennie ; Huth, Cornelia ; Hutri-Kähönen, Nina ; James, Alan L. ; Jansson, John Olov ; Jhun, Min A. ; Juonala, Markus ; Kinnunen, Leena ; Koistinen, Heikki A. ; Kolcic, Ivana ; Komulainen, Pirjo ; Kuusisto, Johanna ; Kvaløy, Kirsti ; Kähönen, Mika ; Lakka, Timo A. ; Launer, Lenore J. ; Lehne, Benjamin ; Lindgren, Cecilia M. ; Lorentzon, Mattias ; Luben, Robert N ; Marre, Michel ; Milaneschi, Yuri ; Monda, Keri L. ; Montgomery, Grant W. ; De Moor, Marleen H.M. ; Mulas, Antonella ; Müller-Nurasyid, Martina ; Musk, A. W. ; Männikkö, Reija ; Männistö, Satu ; Narisu, Narisu ; Nauck, Matthias ; Nettleton, Jennifer A. ; Nolte, Ilja M. ; Oldehinkel, Albertine J. ; Olden, Matthias ; Ong, Ken K. ; Padmanabhan, Sandosh ; Paternoster, Lavinia ; Perez, Jeremiah ; Perola, Markus ; Peters, Annette ; Peters, Ulrike ; Peyser, Patricia A. ; Prokopenko, Inga ; Puolijoki, Hannu ; Raitakari, Olli T. ; Rankinen, Tuomo ; Rasmussen-Torvik, Laura J. ; Rawal, Rajesh ; Ridker, Paul M. ; Rose, Lynda M. ; Rudan, Igor ; Sarti, Cinzia ; Sarzynski, Mark A. ; Savonen, Kai ; Scott, William R. ; Sanna, Serena ; Shuldiner, Alan R. ; Sidney, Steve ; Silbernagel, Günther ; Smith, Blair H. ; Smith, Jennifer A. ; Snieder, Harold ; Stančáková, Alena ; Sternfeld, Barbara ; Swift, Amy J. ; Tammelin, Tuija ; Tan, Sian Tsung ; Thorand, Barbara ; Thuillier, Dorothée ; Vandenput, Liesbeth ; Vestergaard, Henrik ; Van Vliet-Ostaptchouk, Jana V. ; Vohl, Marie Claude ; Völker, Uwe ; Waeber, Gérard ; Walker, Mark ; Wild, Sarah H. ; Wong, Andrew ; Wright, Alan F. ; Zillikens, M. Carola ; Zubair, Niha ; Haiman, Christopher A. ; Lemarchand, Loic ; Gyllensten, Ulf ; Ohlsson, Claes ; Hofman, Albert ; Rivadeneira, Fernando ; Uitterlinden, André G. ; Pérusse, Louis ; Wilson, James F. ; Hayward, Caroline ; Polasek, Ozren ; Cucca, Francesco ; Hveem, Kristian ; Hartman, Catharina A. ; Tönjes, Anke ; Bandinelli, Stefania ; Palmer, Lyle J. ; Kardia, Sharon L R ; Rauramaa, Rainer ; Sørensen, Thorkild I A ; Tuomilehto, Jaakko ; Salomaa, Veikko ; Penninx, Brenda W J H ; De Geus, Eco J C N ; Boomsma, Dorret I. ; Lehtimäki, Terho ; Mangino, Massimo ; Laakso, Markku ; Bouchard, Claude ; Martin, Nicholas G. ; Kuh, Diana ; Liu, Yongmei ; Linneberg, Allan ; März, Winfried ; Strauch, Konstantin ; Kivimäki, Mika ; Harris, Tamara B. ; Gudnason, Vilmundur ; Völzke, Henry ; Qi, Lu ; Järvelin, Marjo Riitta ; Chambers, John C. ; Kooner, Jaspal S. ; Froguel, Philippe ; Kooperberg, Charles ; Vollenweider, Peter ; CHARGE consortium ; EPIC-InterAct Consortium ; PAGE Consortium. / Genome-wide physical activity interactions in adiposity ― A meta-analysis of 200,452 adults. In: PLoS Genetics. 2017 ; Vol. 13, No. 4.
@article{b50073cb559444fdacbef97661940815,
title = "Genome-wide physical activity interactions in adiposity ― A meta-analysis of 200,452 adults",
abstract = "Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23{\%} of participants were categorized as inactive and 77{\%} as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by ~30{\%} in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.",
author = "Mariaelisa Graff and Scott, {Robert A.} and Justice, {Anne E.} and Young, {Kristin L.} and Feitosa, {Mary F.} and Llilda Barata and Winkler, {Thomas W.} and Chu, {Audrey Y.} and Anubha Mahajan and David Hadley and Luting Xue and Tsegaselassie Workalemahu and Heard-Costa, {Nancy L.} and {den Hoed}, Marcel and Ahluwalia, {Tarunveer S.} and Qibin Qi and Ngwa, {Julius S.} and Frida Renstr{\"o}m and Lydia Quaye and Eicher, {John D.} and Hayes, {James E.} and Marilyn Cornelis and Zoltan Kutalik and Elise Lim and Jian’an Luan and Huffman, {Jennifer E.} and Weihua Zhang and Wei Zhao and Griffin, {Paula J.} and Toomas Haller and Shafqat Ahmad and Marques-Vidal, {Pedro M.} and Stephanie Bien and Loic Yengo and Alexander Teumer and Smith, {Albert Vernon} and Meena Kumari and Harder, {Marie Neergaard} and Justesen, {Johanne Marie} and Kleber, {Marcus E.} and Mette Hollensted and Kurt Lohman and Rivera, {Natalia V.} and Whitfield, {John B.} and Zhao, {Jing Hua} and Stringham, {Heather M.} and Lyytik{\"a}inen, {Leo Pekka} and Charlotte Huppertz and Gonneke Willemsen and Peyrot, {Wouter J.} and Ying Wu and Kati Kristiansson and Ayse Demirkan and Myriam Fornage and Maija Hassinen and Bielak, {Lawrence F.} and Gemma Cadby and Toshiko Tanaka and Reedik M{\"a}gi and {Van Der Most}, {Peter J.} and Jackson, {Anne U.} and Bragg-Gresham, {Jennifer L.} and Veronique Vitart and Jonathan Marten and Pau Navarro and Claire Bellis and Dorota Pasko and {\AA}sa Johansson and S{\o}ren Snitker and Cheng, {Ching Yu} and Joel Eriksson and Unhee Lim and Mette Aadahl and Adair, {Linda S.} and Najaf Amin and Beverley Balkau and Juha Auvinen and John Beilby and Bergman, {Richard N.} and Sven Bergmann and Bertoni, {Alain G.} and John Blangero and Am{\'e}lie Bonnefond and Bonnycastle, {Lori L.} and Borja, {Judith B.} and S{\o}ren Brage and Fabio Busonero and Steve Buyske and Harry Campbell and Chines, {Peter S.} and Collins, {Francis S.} and Tanguy Corre and Smith, {George Davey} and Delgado, {Graciela E.} and Nicole Dueker and Marcus D{\"o}rr and Tapani Ebeling and Gudny Eiriksdottir and T{\~o}nu Esko and Faul, {Jessica D.} and Mao Fu and Kristine F{\ae}rch and Christian Gieger and Sven Gl{\"a}ser and Jian Gong and Penny Gordon-Larsen and Harald Grallert and Grammer, {Tanja B.} and Niels Grarup and {van Grootheest}, Gerard and Kennet Harald and Hastie, {Nicholas D.} and Havulinna, {Aki S.} and Hernandez, {Dena G.} and Lucia Hindorff and Hocking, {Lynne J.} and Holmens, {Oddgeir L.} and Christina Holzapfel and Hottenga, {Jouke Jan} and Jie Huang and Tao Huang and Jennie Hui and Cornelia Huth and Nina Hutri-K{\"a}h{\"o}nen and James, {Alan L.} and Jansson, {John Olov} and Jhun, {Min A.} and Markus Juonala and Leena Kinnunen and Koistinen, {Heikki A.} and Ivana Kolcic and Pirjo Komulainen and Johanna Kuusisto and Kirsti Kval{\o}y and Mika K{\"a}h{\"o}nen and Lakka, {Timo A.} and Launer, {Lenore J.} and Benjamin Lehne and Lindgren, {Cecilia M.} and Mattias Lorentzon and Luben, {Robert N} and Michel Marre and Yuri Milaneschi and Monda, {Keri L.} and Montgomery, {Grant W.} and {De Moor}, {Marleen H.M.} and Antonella Mulas and Martina M{\"u}ller-Nurasyid and Musk, {A. W.} and Reija M{\"a}nnikk{\"o} and Satu M{\"a}nnist{\"o} and Narisu Narisu and Matthias Nauck and Nettleton, {Jennifer A.} and Nolte, {Ilja M.} and Oldehinkel, {Albertine J.} and Matthias Olden and Ong, {Ken K.} and Sandosh Padmanabhan and Lavinia Paternoster and Jeremiah Perez and Markus Perola and Annette Peters and Ulrike Peters and Peyser, {Patricia A.} and Inga Prokopenko and Hannu Puolijoki and Raitakari, {Olli T.} and Tuomo Rankinen and Rasmussen-Torvik, {Laura J.} and Rajesh Rawal and Ridker, {Paul M.} and Rose, {Lynda M.} and Igor Rudan and Cinzia Sarti and Sarzynski, {Mark A.} and Kai Savonen and Scott, {William R.} and Serena Sanna and Shuldiner, {Alan R.} and Steve Sidney and G{\"u}nther Silbernagel and Smith, {Blair H.} and Smith, {Jennifer A.} and Harold Snieder and Alena Stanč{\'a}kov{\'a} and Barbara Sternfeld and Swift, {Amy J.} and Tuija Tammelin and Tan, {Sian Tsung} and Barbara Thorand and Doroth{\'e}e Thuillier and Liesbeth Vandenput and Henrik Vestergaard and {Van Vliet-Ostaptchouk}, {Jana V.} and Vohl, {Marie Claude} and Uwe V{\"o}lker and G{\'e}rard Waeber and Mark Walker and Wild, {Sarah H.} and Andrew Wong and Wright, {Alan F.} and Zillikens, {M. Carola} and Niha Zubair and Haiman, {Christopher A.} and Loic Lemarchand and Ulf Gyllensten and Claes Ohlsson and Albert Hofman and Fernando Rivadeneira and Uitterlinden, {Andr{\'e} G.} and Louis P{\'e}russe and Wilson, {James F.} and Caroline Hayward and Ozren Polasek and Francesco Cucca and Kristian Hveem and Hartman, {Catharina A.} and Anke T{\"o}njes and Stefania Bandinelli and Palmer, {Lyle J.} and Kardia, {Sharon L R} and Rainer Rauramaa and S{\o}rensen, {Thorkild I A} and Jaakko Tuomilehto and Veikko Salomaa and Penninx, {Brenda W J H} and {De Geus}, {Eco J C N} and Boomsma, {Dorret I.} and Terho Lehtim{\"a}ki and Massimo Mangino and Markku Laakso and Claude Bouchard and Martin, {Nicholas G.} and Diana Kuh and Yongmei Liu and Allan Linneberg and Winfried M{\"a}rz and Konstantin Strauch and Mika Kivim{\"a}ki and Harris, {Tamara B.} and Vilmundur Gudnason and Henry V{\"o}lzke and Lu Qi and J{\"a}rvelin, {Marjo Riitta} and Chambers, {John C.} and Kooner, {Jaspal S.} and Philippe Froguel and Charles Kooperberg and Peter Vollenweider and {CHARGE consortium} and {EPIC-InterAct Consortium} and {PAGE Consortium}",
year = "2017",
month = "4",
day = "1",
doi = "10.1371/journal.pgen.1006528",
language = "English",
volume = "13",
journal = "PLOS Genetics",
issn = "1553-7390",
publisher = "PUBLIC LIBRARY SCIENCE",
number = "4",

}

Graff, M, Scott, RA, Justice, AE, Young, KL, Feitosa, MF, Barata, L, Winkler, TW, Chu, AY, Mahajan, A, Hadley, D, Xue, L, Workalemahu, T, Heard-Costa, NL, den Hoed, M, Ahluwalia, TS, Qi, Q, Ngwa, JS, Renström, F, Quaye, L, Eicher, JD, Hayes, JE, Cornelis, M, Kutalik, Z, Lim, E, Luan, J, Huffman, JE, Zhang, W, Zhao, W, Griffin, PJ, Haller, T, Ahmad, S, Marques-Vidal, PM, Bien, S, Yengo, L, Teumer, A, Smith, AV, Kumari, M, Harder, MN, Justesen, JM, Kleber, ME, Hollensted, M, Lohman, K, Rivera, NV, Whitfield, JB, Zhao, JH, Stringham, HM, Lyytikäinen, LP, Huppertz, C, Willemsen, G, Peyrot, WJ, Wu, Y, Kristiansson, K, Demirkan, A, Fornage, M, Hassinen, M, Bielak, LF, Cadby, G, Tanaka, T, Mägi, R, Van Der Most, PJ, Jackson, AU, Bragg-Gresham, JL, Vitart, V, Marten, J, Navarro, P, Bellis, C, Pasko, D, Johansson, Å, Snitker, S, Cheng, CY, Eriksson, J, Lim, U, Aadahl, M, Adair, LS, Amin, N, Balkau, B, Auvinen, J, Beilby, J, Bergman, RN, Bergmann, S, Bertoni, AG, Blangero, J, Bonnefond, A, Bonnycastle, LL, Borja, JB, Brage, S, Busonero, F, Buyske, S, Campbell, H, Chines, PS, Collins, FS, Corre, T, Smith, GD, Delgado, GE, Dueker, N, Dörr, M, Ebeling, T, Eiriksdottir, G, Esko, T, Faul, JD, Fu, M, Færch, K, Gieger, C, Gläser, S, Gong, J, Gordon-Larsen, P, Grallert, H, Grammer, TB, Grarup, N, van Grootheest, G, Harald, K, Hastie, ND, Havulinna, AS, Hernandez, DG, Hindorff, L, Hocking, LJ, Holmens, OL, Holzapfel, C, Hottenga, JJ, Huang, J, Huang, T, Hui, J, Huth, C, Hutri-Kähönen, N, James, AL, Jansson, JO, Jhun, MA, Juonala, M, Kinnunen, L, Koistinen, HA, Kolcic, I, Komulainen, P, Kuusisto, J, Kvaløy, K, Kähönen, M, Lakka, TA, Launer, LJ, Lehne, B, Lindgren, CM, Lorentzon, M, Luben, RN, Marre, M, Milaneschi, Y, Monda, KL, Montgomery, GW, De Moor, MHM, Mulas, A, Müller-Nurasyid, M, Musk, AW, Männikkö, R, Männistö, S, Narisu, N, Nauck, M, Nettleton, JA, Nolte, IM, Oldehinkel, AJ, Olden, M, Ong, KK, Padmanabhan, S, Paternoster, L, Perez, J, Perola, M, Peters, A, Peters, U, Peyser, PA, Prokopenko, I, Puolijoki, H, Raitakari, OT, Rankinen, T, Rasmussen-Torvik, LJ, Rawal, R, Ridker, PM, Rose, LM, Rudan, I, Sarti, C, Sarzynski, MA, Savonen, K, Scott, WR, Sanna, S, Shuldiner, AR, Sidney, S, Silbernagel, G, Smith, BH, Smith, JA, Snieder, H, Stančáková, A, Sternfeld, B, Swift, AJ, Tammelin, T, Tan, ST, Thorand, B, Thuillier, D, Vandenput, L, Vestergaard, H, Van Vliet-Ostaptchouk, JV, Vohl, MC, Völker, U, Waeber, G, Walker, M, Wild, SH, Wong, A, Wright, AF, Zillikens, MC, Zubair, N, Haiman, CA, Lemarchand, L, Gyllensten, U, Ohlsson, C, Hofman, A, Rivadeneira, F, Uitterlinden, AG, Pérusse, L, Wilson, JF, Hayward, C, Polasek, O, Cucca, F, Hveem, K, Hartman, CA, Tönjes, A, Bandinelli, S, Palmer, LJ, Kardia, SLR, Rauramaa, R, Sørensen, TIA, Tuomilehto, J, Salomaa, V, Penninx, BWJH, De Geus, EJCN, Boomsma, DI, Lehtimäki, T, Mangino, M, Laakso, M, Bouchard, C, Martin, NG, Kuh, D, Liu, Y, Linneberg, A, März, W, Strauch, K, Kivimäki, M, Harris, TB, Gudnason, V, Völzke, H, Qi, L, Järvelin, MR, Chambers, JC, Kooner, JS, Froguel, P, Kooperberg, C, Vollenweider, P, CHARGE consortium, EPIC-InterAct Consortium & PAGE Consortium 2017, 'Genome-wide physical activity interactions in adiposity ― A meta-analysis of 200,452 adults' PLoS Genetics, vol 13, no. 4, e1006528. DOI: 10.1371/journal.pgen.1006528

Genome-wide physical activity interactions in adiposity ― A meta-analysis of 200,452 adults. / Graff, Mariaelisa; Scott, Robert A.; Justice, Anne E.; Young, Kristin L.; Feitosa, Mary F.; Barata, Llilda; Winkler, Thomas W.; Chu, Audrey Y.; Mahajan, Anubha; Hadley, David; Xue, Luting; Workalemahu, Tsegaselassie; Heard-Costa, Nancy L.; den Hoed, Marcel; Ahluwalia, Tarunveer S.; Qi, Qibin; Ngwa, Julius S.; Renström, Frida; Quaye, Lydia; Eicher, John D.; Hayes, James E.; Cornelis, Marilyn; Kutalik, Zoltan; Lim, Elise; Luan, Jian’an; Huffman, Jennifer E.; Zhang, Weihua; Zhao, Wei; Griffin, Paula J.; Haller, Toomas; Ahmad, Shafqat; Marques-Vidal, Pedro M.; Bien, Stephanie; Yengo, Loic; Teumer, Alexander; Smith, Albert Vernon; Kumari, Meena; Harder, Marie Neergaard; Justesen, Johanne Marie; Kleber, Marcus E.; Hollensted, Mette; Lohman, Kurt; Rivera, Natalia V.; Whitfield, John B.; Zhao, Jing Hua; Stringham, Heather M.; Lyytikäinen, Leo Pekka; Huppertz, Charlotte; Willemsen, Gonneke; Peyrot, Wouter J.; Wu, Ying; Kristiansson, Kati; Demirkan, Ayse; Fornage, Myriam; Hassinen, Maija; Bielak, Lawrence F.; Cadby, Gemma; Tanaka, Toshiko; Mägi, Reedik; Van Der Most, Peter J.; Jackson, Anne U.; Bragg-Gresham, Jennifer L.; Vitart, Veronique; Marten, Jonathan; Navarro, Pau; Bellis, Claire; Pasko, Dorota; Johansson, Åsa; Snitker, Søren; Cheng, Ching Yu; Eriksson, Joel; Lim, Unhee; Aadahl, Mette; Adair, Linda S.; Amin, Najaf; Balkau, Beverley; Auvinen, Juha; Beilby, John; Bergman, Richard N.; Bergmann, Sven; Bertoni, Alain G.; Blangero, John; Bonnefond, Amélie; Bonnycastle, Lori L.; Borja, Judith B.; Brage, Søren; Busonero, Fabio; Buyske, Steve; Campbell, Harry; Chines, Peter S.; Collins, Francis S.; Corre, Tanguy; Smith, George Davey; Delgado, Graciela E.; Dueker, Nicole; Dörr, Marcus; Ebeling, Tapani; Eiriksdottir, Gudny; Esko, Tõnu; Faul, Jessica D.; Fu, Mao; Færch, Kristine; Gieger, Christian; Gläser, Sven; Gong, Jian; Gordon-Larsen, Penny; Grallert, Harald; Grammer, Tanja B.; Grarup, Niels; van Grootheest, Gerard; Harald, Kennet; Hastie, Nicholas D.; Havulinna, Aki S.; Hernandez, Dena G.; Hindorff, Lucia; Hocking, Lynne J.; Holmens, Oddgeir L.; Holzapfel, Christina; Hottenga, Jouke Jan; Huang, Jie; Huang, Tao; Hui, Jennie; Huth, Cornelia; Hutri-Kähönen, Nina; James, Alan L.; Jansson, John Olov; Jhun, Min A.; Juonala, Markus; Kinnunen, Leena; Koistinen, Heikki A.; Kolcic, Ivana; Komulainen, Pirjo; Kuusisto, Johanna; Kvaløy, Kirsti; Kähönen, Mika; Lakka, Timo A.; Launer, Lenore J.; Lehne, Benjamin; Lindgren, Cecilia M.; Lorentzon, Mattias; Luben, Robert N; Marre, Michel; Milaneschi, Yuri; Monda, Keri L.; Montgomery, Grant W.; De Moor, Marleen H.M.; Mulas, Antonella; Müller-Nurasyid, Martina; Musk, A. W.; Männikkö, Reija; Männistö, Satu; Narisu, Narisu; Nauck, Matthias; Nettleton, Jennifer A.; Nolte, Ilja M.; Oldehinkel, Albertine J.; Olden, Matthias; Ong, Ken K.; Padmanabhan, Sandosh; Paternoster, Lavinia; Perez, Jeremiah; Perola, Markus; Peters, Annette; Peters, Ulrike; Peyser, Patricia A.; Prokopenko, Inga; Puolijoki, Hannu; Raitakari, Olli T.; Rankinen, Tuomo; Rasmussen-Torvik, Laura J.; Rawal, Rajesh; Ridker, Paul M.; Rose, Lynda M.; Rudan, Igor; Sarti, Cinzia; Sarzynski, Mark A.; Savonen, Kai; Scott, William R.; Sanna, Serena; Shuldiner, Alan R.; Sidney, Steve; Silbernagel, Günther; Smith, Blair H.; Smith, Jennifer A.; Snieder, Harold; Stančáková, Alena; Sternfeld, Barbara; Swift, Amy J.; Tammelin, Tuija; Tan, Sian Tsung; Thorand, Barbara; Thuillier, Dorothée; Vandenput, Liesbeth; Vestergaard, Henrik; Van Vliet-Ostaptchouk, Jana V.; Vohl, Marie Claude; Völker, Uwe; Waeber, Gérard; Walker, Mark; Wild, Sarah H.; Wong, Andrew; Wright, Alan F.; Zillikens, M. Carola; Zubair, Niha; Haiman, Christopher A.; Lemarchand, Loic; Gyllensten, Ulf; Ohlsson, Claes; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, André G.; Pérusse, Louis; Wilson, James F.; Hayward, Caroline; Polasek, Ozren; Cucca, Francesco; Hveem, Kristian; Hartman, Catharina A.; Tönjes, Anke; Bandinelli, Stefania; Palmer, Lyle J.; Kardia, Sharon L R; Rauramaa, Rainer; Sørensen, Thorkild I A; Tuomilehto, Jaakko; Salomaa, Veikko; Penninx, Brenda W J H; De Geus, Eco J C N; Boomsma, Dorret I.; Lehtimäki, Terho; Mangino, Massimo; Laakso, Markku; Bouchard, Claude; Martin, Nicholas G.; Kuh, Diana; Liu, Yongmei; Linneberg, Allan; März, Winfried; Strauch, Konstantin; Kivimäki, Mika; Harris, Tamara B.; Gudnason, Vilmundur; Völzke, Henry; Qi, Lu; Järvelin, Marjo Riitta; Chambers, John C.; Kooner, Jaspal S.; Froguel, Philippe; Kooperberg, Charles; Vollenweider, Peter; CHARGE consortium; EPIC-InterAct Consortium; PAGE Consortium.

In: PLoS Genetics, Vol. 13, No. 4, e1006528, 01.04.2017.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genome-wide physical activity interactions in adiposity ― A meta-analysis of 200,452 adults

AU - Graff,Mariaelisa

AU - Scott,Robert A.

AU - Justice,Anne E.

AU - Young,Kristin L.

AU - Feitosa,Mary F.

AU - Barata,Llilda

AU - Winkler,Thomas W.

AU - Chu,Audrey Y.

AU - Mahajan,Anubha

AU - Hadley,David

AU - Xue,Luting

AU - Workalemahu,Tsegaselassie

AU - Heard-Costa,Nancy L.

AU - den Hoed,Marcel

AU - Ahluwalia,Tarunveer S.

AU - Qi,Qibin

AU - Ngwa,Julius S.

AU - Renström,Frida

AU - Quaye,Lydia

AU - Eicher,John D.

AU - Hayes,James E.

AU - Cornelis,Marilyn

AU - Kutalik,Zoltan

AU - Lim,Elise

AU - Luan,Jian’an

AU - Huffman,Jennifer E.

AU - Zhang,Weihua

AU - Zhao,Wei

AU - Griffin,Paula J.

AU - Haller,Toomas

AU - Ahmad,Shafqat

AU - Marques-Vidal,Pedro M.

AU - Bien,Stephanie

AU - Yengo,Loic

AU - Teumer,Alexander

AU - Smith,Albert Vernon

AU - Kumari,Meena

AU - Harder,Marie Neergaard

AU - Justesen,Johanne Marie

AU - Kleber,Marcus E.

AU - Hollensted,Mette

AU - Lohman,Kurt

AU - Rivera,Natalia V.

AU - Whitfield,John B.

AU - Zhao,Jing Hua

AU - Stringham,Heather M.

AU - Lyytikäinen,Leo Pekka

AU - Huppertz,Charlotte

AU - Willemsen,Gonneke

AU - Peyrot,Wouter J.

AU - Wu,Ying

AU - Kristiansson,Kati

AU - Demirkan,Ayse

AU - Fornage,Myriam

AU - Hassinen,Maija

AU - Bielak,Lawrence F.

AU - Cadby,Gemma

AU - Tanaka,Toshiko

AU - Mägi,Reedik

AU - Van Der Most,Peter J.

AU - Jackson,Anne U.

AU - Bragg-Gresham,Jennifer L.

AU - Vitart,Veronique

AU - Marten,Jonathan

AU - Navarro,Pau

AU - Bellis,Claire

AU - Pasko,Dorota

AU - Johansson,Åsa

AU - Snitker,Søren

AU - Cheng,Ching Yu

AU - Eriksson,Joel

AU - Lim,Unhee

AU - Aadahl,Mette

AU - Adair,Linda S.

AU - Amin,Najaf

AU - Balkau,Beverley

AU - Auvinen,Juha

AU - Beilby,John

AU - Bergman,Richard N.

AU - Bergmann,Sven

AU - Bertoni,Alain G.

AU - Blangero,John

AU - Bonnefond,Amélie

AU - Bonnycastle,Lori L.

AU - Borja,Judith B.

AU - Brage,Søren

AU - Busonero,Fabio

AU - Buyske,Steve

AU - Campbell,Harry

AU - Chines,Peter S.

AU - Collins,Francis S.

AU - Corre,Tanguy

AU - Smith,George Davey

AU - Delgado,Graciela E.

AU - Dueker,Nicole

AU - Dörr,Marcus

AU - Ebeling,Tapani

AU - Eiriksdottir,Gudny

AU - Esko,Tõnu

AU - Faul,Jessica D.

AU - Fu,Mao

AU - Færch,Kristine

AU - Gieger,Christian

AU - Gläser,Sven

AU - Gong,Jian

AU - Gordon-Larsen,Penny

AU - Grallert,Harald

AU - Grammer,Tanja B.

AU - Grarup,Niels

AU - van Grootheest,Gerard

AU - Harald,Kennet

AU - Hastie,Nicholas D.

AU - Havulinna,Aki S.

AU - Hernandez,Dena G.

AU - Hindorff,Lucia

AU - Hocking,Lynne J.

AU - Holmens,Oddgeir L.

AU - Holzapfel,Christina

AU - Hottenga,Jouke Jan

AU - Huang,Jie

AU - Huang,Tao

AU - Hui,Jennie

AU - Huth,Cornelia

AU - Hutri-Kähönen,Nina

AU - James,Alan L.

AU - Jansson,John Olov

AU - Jhun,Min A.

AU - Juonala,Markus

AU - Kinnunen,Leena

AU - Koistinen,Heikki A.

AU - Kolcic,Ivana

AU - Komulainen,Pirjo

AU - Kuusisto,Johanna

AU - Kvaløy,Kirsti

AU - Kähönen,Mika

AU - Lakka,Timo A.

AU - Launer,Lenore J.

AU - Lehne,Benjamin

AU - Lindgren,Cecilia M.

AU - Lorentzon,Mattias

AU - Luben,Robert N

AU - Marre,Michel

AU - Milaneschi,Yuri

AU - Monda,Keri L.

AU - Montgomery,Grant W.

AU - De Moor,Marleen H.M.

AU - Mulas,Antonella

AU - Müller-Nurasyid,Martina

AU - Musk,A. W.

AU - Männikkö,Reija

AU - Männistö,Satu

AU - Narisu,Narisu

AU - Nauck,Matthias

AU - Nettleton,Jennifer A.

AU - Nolte,Ilja M.

AU - Oldehinkel,Albertine J.

AU - Olden,Matthias

AU - Ong,Ken K.

AU - Padmanabhan,Sandosh

AU - Paternoster,Lavinia

AU - Perez,Jeremiah

AU - Perola,Markus

AU - Peters,Annette

AU - Peters,Ulrike

AU - Peyser,Patricia A.

AU - Prokopenko,Inga

AU - Puolijoki,Hannu

AU - Raitakari,Olli T.

AU - Rankinen,Tuomo

AU - Rasmussen-Torvik,Laura J.

AU - Rawal,Rajesh

AU - Ridker,Paul M.

AU - Rose,Lynda M.

AU - Rudan,Igor

AU - Sarti,Cinzia

AU - Sarzynski,Mark A.

AU - Savonen,Kai

AU - Scott,William R.

AU - Sanna,Serena

AU - Shuldiner,Alan R.

AU - Sidney,Steve

AU - Silbernagel,Günther

AU - Smith,Blair H.

AU - Smith,Jennifer A.

AU - Snieder,Harold

AU - Stančáková,Alena

AU - Sternfeld,Barbara

AU - Swift,Amy J.

AU - Tammelin,Tuija

AU - Tan,Sian Tsung

AU - Thorand,Barbara

AU - Thuillier,Dorothée

AU - Vandenput,Liesbeth

AU - Vestergaard,Henrik

AU - Van Vliet-Ostaptchouk,Jana V.

AU - Vohl,Marie Claude

AU - Völker,Uwe

AU - Waeber,Gérard

AU - Walker,Mark

AU - Wild,Sarah H.

AU - Wong,Andrew

AU - Wright,Alan F.

AU - Zillikens,M. Carola

AU - Zubair,Niha

AU - Haiman,Christopher A.

AU - Lemarchand,Loic

AU - Gyllensten,Ulf

AU - Ohlsson,Claes

AU - Hofman,Albert

AU - Rivadeneira,Fernando

AU - Uitterlinden,André G.

AU - Pérusse,Louis

AU - Wilson,James F.

AU - Hayward,Caroline

AU - Polasek,Ozren

AU - Cucca,Francesco

AU - Hveem,Kristian

AU - Hartman,Catharina A.

AU - Tönjes,Anke

AU - Bandinelli,Stefania

AU - Palmer,Lyle J.

AU - Kardia,Sharon L R

AU - Rauramaa,Rainer

AU - Sørensen,Thorkild I A

AU - Tuomilehto,Jaakko

AU - Salomaa,Veikko

AU - Penninx,Brenda W J H

AU - De Geus,Eco J C N

AU - Boomsma,Dorret I.

AU - Lehtimäki,Terho

AU - Mangino,Massimo

AU - Laakso,Markku

AU - Bouchard,Claude

AU - Martin,Nicholas G.

AU - Kuh,Diana

AU - Liu,Yongmei

AU - Linneberg,Allan

AU - März,Winfried

AU - Strauch,Konstantin

AU - Kivimäki,Mika

AU - Harris,Tamara B.

AU - Gudnason,Vilmundur

AU - Völzke,Henry

AU - Qi,Lu

AU - Järvelin,Marjo Riitta

AU - Chambers,John C.

AU - Kooner,Jaspal S.

AU - Froguel,Philippe

AU - Kooperberg,Charles

AU - Vollenweider,Peter

AU - CHARGE consortium

AU - EPIC-InterAct Consortium

AU - PAGE Consortium

PY - 2017/4/1

Y1 - 2017/4/1

N2 - Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by ~30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.

AB - Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by ~30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.

UR - http://www.scopus.com/inward/record.url?scp=85018450983&partnerID=8YFLogxK

U2 - 10.1371/journal.pgen.1006528

DO - 10.1371/journal.pgen.1006528

M3 - Article

VL - 13

JO - PLOS Genetics

T2 - PLOS Genetics

JF - PLOS Genetics

SN - 1553-7390

IS - 4

M1 - e1006528

ER -

Graff M, Scott RA, Justice AE, Young KL, Feitosa MF, Barata L et al. Genome-wide physical activity interactions in adiposity ― A meta-analysis of 200,452 adults. PLoS Genetics. 2017 Apr 1;13(4). e1006528. Available from, DOI: 10.1371/journal.pgen.1006528