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151. Distinct Roles of Dietary Fat and Sugar in the Development of Obesity, Insulin Resistance, Atherosclerosis and Cardiac Dysfunction in LDL Receptor Knockout Mice

Author

Perazza, Laís R., Daniel, Noemie, Dubois, Marie Julie, Pilon, Geneviève, Mitchell, Patricia, Le Quang, Khai, Lachance, Dominic, Plante, Eric, Varin, Thibaut, Bouchareb, Rihab, Boyer, Marjorie, Arsenault, Benoît, Mathieu, Patrick, Gauthier, Sylvie, Pouliot, Yves, Roy, Denis, and Marette, André

Published
2018
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153. Activation of p38 Mitogen-Activated Protein Kinase [Alpha] and [Beta] by Insulin and Contraction in Rat Skeletal Muscle

Author

Somwar, Romel, Perreault, Mylene, Kapur, Sonia, Taha, Celia, Sweeney, Gary, Ramlal, Toolsie, Kim, David Y., Keen, Jessica, Cote, Claude H., Klip, Amira, and Marette, Andre

Subjects
Diabetes -- Research, Glucose metabolism -- Physiological aspects, Health
Abstract

Potential Role in the Stimulation of Glucose Transport The stress-activated p38 mitogen-activated protein kinase (MAPK) was recently shown to be activated by insulin in muscle and adipose cells in culture. [...]

Published
2000

154. Sustained Activation of Insulin Receptors Internalized in GLUT4 Vesicles of Insulin-Stimulated Skeletal Muscle

Author

Dombrowski, Luce, Faure, Robert, and Marette, Andre

Subjects
Insulin -- Receptors, Diabetes -- Research, Glucose metabolism -- Physiological aspects, Health
Abstract

Exposure of target cells to insulin results in the formation of ligand receptor complexes on the cell surface and their subsequent internalization into the endosomal apparatus. A current view is [...]

Published
2000

155. Activation of p38 Mitogen-Activated Protein Kinase Alpha and Beta Isoforms by Insulin in Rat Skeletal Muscle: Participation in the Stimulation of Glucose Transport

Author

SOMWAR, ROMEL, PERREAULT, MYLENE, KAPUR, SONIA, TAHA, CELIA, KIM, DAVID Y., SWEENEY, GARY, RAMLAL, TOOLSIE, COTE, CLAUDE H., KLIP, AMIRA, and MARETTE, ANDRE

Subjects
Protein kinases -- Physiological aspects, Glucose metabolism -- Models, Health
Abstract

We have previously shown that SB203580, an inhibitor of p38 mitogen-activated protein kinase (p38MAPK), attenuated insulin-stimulated glucose uptake in L6 skeletal muscle cells and 3T3-L1 adipocytes. Here we further explore [...]

Published
2000

156. The Transferrin Receptor Defines Two Distinct Contraction-Responsive GLUT4 Vesicle Populations in Skeletal Muscle

Author

Lemieux, Kathleen, Han, Xiao-Xia, Dombrowski, Luce, Bonen, Arend, and Marette, Andre

Subjects
Biological transport -- Research -- Physiological aspects, Diabetes -- Research, Insulin -- Research, Glucose metabolism -- Physiological aspects -- Research, Health, Physiological aspects, Research
Abstract

Insulin and contraction increase glucose transport in an additive fashion in skeletal muscle. However, it is still unclear whether they do so by inducing the recruitment of GLUT4 transporters from [...]

Published
2000

157. Genetic studies of body mass index yield new insights for obesity biology

Author

Locke, Adam E., Kahali, Bratati, Berndt, Sonja I., Justice, Anne E., Pers, Tune H., Day, Felix R., Powell, Corey, Vedantam, Sailaja, Buchkovich, Martin L., Yang, Jian, Croteau-Chonka, Damien C., Esko, Tonu, Fall, Tove, Ferreira, Teresa, Gustafsson, Stefan, Kutalik, Zoltan, Luan, Jian'an, Maegi, Reedik, Randall, Joshua C., Winkler, Thomas W., Wood, Andrew R., Workalemahu, Tsegaselassie, Faul, Jessica D., Smith, Jennifer A., Zhao, Jing Hua, Zhao, Wei, Chen, Jin, Fehrmann, Rudolf, Hedman, Asa K., Karjalainen, Juha, Schmidt, Ellen M., Absher, Devin, Amin, Najaf, Anderson, Denise, Beekman, Marian, Bolton, Jennifer L., Bragg-Gresham, L., Buyske, Steven, Demirkan, Ayse, Deng, Guohong, Ehret, Georg B., Feenstra, Bjarke, Feitosa, Mary F., Fischer, Krista, Goel, Anuj, Gong, Jian, Jackson, Anne U., Kanoni, Stavroula, Kleber, Marcus E., Kristiansson, Kati, Lim, Unhee, Lotay, Vaneet, Mangino, Massimo, Leach, Irene Mateo, Medina-Gomez, Carolina, Medland, Sarah E., Nalls, Michael A., Palmer, Cameron D., Pasko, Dorota, Pechlivanis, Sonali, Peters, Marjolein J., Prokopenko, Inga, Shungin, Dmitry, Stancakova, Alena, Strawbridge, Rona J., Sung, Yun Ju, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, van der Laan, Sander W., van Settee, Jessica, Van Vliet-Ostaptchouk, Jana V., Wang, Zhaoming, Yengo, Loic, Zhang, Weihua, Isaacs, Aaron, Albrecht, Eva, Arnlov, Johan, Arscott, Gillian M., Attwood, Antony P., Bandinelli, Stefania, Barrett, Amy, Bas, Isabelita N., Bellis, Claire, Bennett, Amanda J., Berne, Christian, Blagieva, Roza, Blueher, Matthias, Bohringer, Stefan, Bonnycastle, Lori L., Boettcher, Yvonne, Boyd, Heather A., Bruinenberg, Marcel, Caspersen, Ida H., Chen, Yii-Der Ida, Clarke, Robert, Daw, E. Warwick, de Craen, Anton J. M., Delgado, Graciela, Dimitriou, Maria, Doney, Alex S. F., Eklund, Niina, Estrada, Karol, Eury, Elodie, Folkersen, Lasse, Fraser, Ross M., Garcia, Melissa E., Geller, Frank, Giedraitis, Vilmantas, Gigante, Bruna, Go, Alan S., Golay, Alain, Goodall, Alison H., Gordon, Scott D., Gorski, Mathias, Grabe, Hans-Joergen, Grallert, Harald, Grammer, Tanja B., Graessler, Jurgen, Gronberg, Henrik, Groves, Christopher J., Gusto, Gaeelle, Haessler, Jeffrey, Hall, Per, Haller, Toomas, Hallmans, Göran, Hartman, Catharina A., Hassinen, Maija, Hayward, Caroline, Heard-Costa, Nancy L., Helmer, Qinta, Hengstenberg, Christian, Holmen, Oddgeir, Hottenga, Jouke-Jan, James, Alan L., Jeff, Janina M., Johansson, Asa, Jolley, Jennifer, Juliusdottir, Thorhildur, Kinnunen, Leena, Koenig, Wolfgang, Koskenvuo, Markku, Kratzer, Wolfgang, Laitinen, Jaana, Lamina, Claudia, Leander, Karin, Lee, Nanette R., Lichtner, Peter, Lind, Lars, Lindstrom, Jaana, Lo, Ken Sin, Lobbens, Stephane, Lorbeer, Roberto, Lu, Yingchang, Mach, Francois, Magnusson, Patrik K. E., Mahajan, Anubha, McArdle, Wendy L., McLachlan, Stela, Menni, Cristina, Merger, Sigrun, Mihailov, Evelin, Milani, Lili, Moayyeri, Alireza, Monda, Keri L., Morken, Mario A., Mulas, Antonella, Mueller, Gabriele, Mueller-Nurasyid, Martina, Musk, Arthur W., Nagaraja, Ramaiah, Noethen, Markus M., Nolte, Ilja M., Pilz, Stefan, Rayner, Nigel W., Renstrom, Frida, Rettig, Rainer, Ried, Janina S., Ripke, Stephan, Robertson, Neil R., Rose, Lynda M., Sanna, Serena, Scharnagl, Hubert, Scholtens, Salome, Schumacher, Fredrick R., Scott, William R., Seufferlein, Thomas, Shi, Jianxin, Smith, Albert Vernon, Smolonska, Joanna, Stanton, Alice V., Steinthorsdottir, Valgerdur, Stirrups, Kathleen, Stringham, Heather M., Sundstrom, Johan, Swertz, Morris A., Swift, Amy J., Syvanen, Ann-Christine, Tan, Sian-Tsung, Tayo, Bamidele O., Thorand, Barbara, Thorleifsson, Gudmar, Tyrer, Jonathan P., Uh, Hae-Won, Vandenput, Liesbeth, Verhulst, Frank C., Vermeulen, Sita H., Verweij, Niek, Vonk, Judith M., Waite, Lindsay L., Warren, Helen R., Waterworth, Dawn, Weedon, Michael N., Wilkens, Lynne R., Willenborg, Christina, Wilsgaard, Tom, Wojczynski, Mary K., Wong, Andrew, Wrightl, Alan F., Zhang, Qunyuan, Brennan, Eoin P., Choi, Murim, Dastani, Zari, Drong, Alexander W., Eriksson, Per, Franco-Cereceda, Anders, Gadin, Jesper R., Gharavi, Ali G., Goddard, Michael E., Handsaker, Robert E., Huang, Jinyan, Karpe, Fredrik, Kathiresan, Sekar, Keildson, Sarah, Kiryluk, Krzysztof, Kubo, Michiaki, Lee, Jong-Young, Liang, Liming, Lifton, Richard P., Ma, Baoshan, McCarroll, Steven A., McKnight, Amy J., Min, Josine L., Moffatt, Miriam F., Montgomery, Grant W., Murabito, Joanne M., Nicholson, George, Nyholt, Dale R., Okada, Yukinori, Perry, John R. B., Dorajoo, Rajkumar, Reinmaa, Eva, Salem, Rany M., Sandholm, Niina, Scott, Robert A., Stolk, Lisette, Takahashi, Atsushi, Tanaka, Toshihiro, van 't Hooft, Ferdinand M., Vinkhuyzen, Anna A. E., Westra, Harm-Jan, Zheng, Wei, Zondervan, Krina T., Heath, Andrew C., Arveiler, Dominique, Bakker, Stephan J. L., Beilby, John, Bergman, Richard N., Blangero, John, Bovet, Pascal, Campbell, Harry, Caulfield, Mark J., Cesana, Giancarlo, Chakravarti, Aravinda, Chasman, Daniel I., Chines, Peter S., Collins, Francis S., Crawford, Dana C., Cupples, L. Adrienne, Cusi, Daniele, Danesh, John, de Faire, Ulf, den Ruijter, Hester M., Dominiczak, Anna F., Erbel, Raimund, Erdmann, Jeanette, Eriksson, Johan G., Farrall, Martin, Felix, Stephan B., Ferrannini, Ele, Ferrieres, Jean, Ford, Ian, Forouhi, Nita G., Forrester, Terrence, Franco, Oscar H., Gansevoort, Ron T., Gejman, Pablo V., Gieger, Christian, Gottesman, Omri, Gudnason, Vilmundur, Gyllensten, Ulf, Hall, Alistair S., Harris, Tamara B., Hattersley, Andrew T., Hicks, Andrew A., Hindorff, Lucia A., Hingorani, Aroon D., Hofman, Albert, Homuth, Georg, Hovingh, G. Kees, Humphries, Steve E., Hunt, Steven C., Hypponen, Elina, Illig, Thomas, Jacobs, Kevin B., Jarvelin, Marjo-Riitta, Joeckel, Karl-Heinz, Johansen, Berit, Jousilahti, Pekka, Jukema, J. Wouter, Jula, Antti M., Kaprio, Jaakko, Kastelein, John J. P., Keinanen-Kiukaanniemi, Sirkka M., Kiemeney, Lambertus A., Knekt, Paul, Kooner, Jaspal S., Kooperberg, Charles, Kovacs, Peter, Kraja, Aldi T., Kumari, Meena, Kuusisto, Johanna, Lakka, Timo A., Langenberg, Claudia, Le Marchand, Laic, Lehtimaki, Terho, Lyssenko, Valeriya, Mannisto, Satu, Marette, Andre, Matise, Tara C., McKenzie, Colin A., McKnight, Barbara, Moll, Frans L., Morris, Andrew D., Morris, Andrew P., Murray, Jeffrey C., Nelis, Mari, Ohlsson, Claes, Oldehinkel, Albertine J., Ong, Ken K., Madden, Pamela A. F., Pasterkamp, Gerard, Peden, John F., Peters, Annette, Postma, Dirkje S., Pramstaller, Peter P., Price, Jackie F., Qi, Lu, Raitakari, Olli T., Rankinen, Tuomo, Rao, D. C., Rice, Treva K., Ridker, Paul M., Rioux, John D., Ritchie, Marylyn D., Rudan, Igor, Salomaa, Veikko, Samani, Nilesh J., Saramines, Jouko, Sarzynski, Mark A., Schunkert, Heribert, Schwarz, Peter E. H., Sever, Peter, Shuldiner, Alan R., Sinisalo, Juha, Stolk, Ronald P., Strauch, Konstantin, Toenjes, Anke, Tregouet, David-Alexandre, Tremblay, Angelo, Tremoli, Elena, Virtamo, Jarmo, Vohl, Marie-Claude, Voelker, Uwe, Waeber, Gerard, Willemsen, Gonneke, Witteman, Jacqueline C., Zillikens, M. Carola, Adair, Linda S., Amouyel, Philippe, Asselbergs, Folkert W., Assimes, Themistocles L., Bochud, Murielle, Boehm, Bernhard O., Boerwinkle, Eric, Bornstein, Stefan R., Bottinger, Erwin P., Bouchard, Claude, Cauchi, Stephane, Chambers, John C., Chanock, Stephen J., Cooper, Richard S., de Bakker, Paul I. W., Dedoussis, George, Ferrucci, Luigi, Franks, Paul W., Froguel, Philippe, Groop, Leif C., Haiman, Christopher A., Hamsten, Anders, Hui, Jennie, Hunter, David J., Hveem, Kristian, Kaplan, Robert C., Kivimaki, Mika, Kuh, Diana, Laakso, Markku, Liu, Yongmei, Martin, Nicholas G., Maerz, Winfried, Melbve, Mads, Metspalu, Andres, Moebus, Susanne, Munroe, Patricia B., Njolstad, Inger, Oostra, Ben A., Palmer, Colin N. A., Pedersen, Nancy L., Perola, Markus, Perusse, Louis, Peters, Ulrike, Power, Chris, Quertermous, Thomas, Rauramaa, Rainer, Rivadeneira, Fernando, Saaristo, Timo E., Saleheen, Danish, Sattar, Naveed, Schadt, Eric E., Schlessinger, David, Slagboom, P. Eline, Snieder, Harold, Spector, Tim D., Thorsteinsdottir, Unnu R., Stumvoll, Michael, Tuomilehto, Jaakko, Uitterlinden, Andre G., Uusitupa, Matti, van der Harst, Pim, Walker, Mark, Wallaschofski, Henri, Wareham, Nicholas J., Watkins, Hugh, Weir, David R., Wichmann, H-Erich, Wilson, James F., Zanen, Pieter, Borecki, Ingrid B., Deloukas, Panos, Fox, Caroline S., Heid, Iris M., O'Connell, Jeffrey R., Strachan, David P., Stefansson, Kari, van Duijri, Cornelia M., Abecasis, Goncalo R., Franke, Lude, Frayling, Timothy M., McCarthy, Mark I., Visscher, Peter M., Scherag, Andre, Willer, Cristen J., Boehnke, Michael, Mohlke, Karen L., Lindgren, Cecilia M., Beckmann, Jacques S., Barroso, Ines, North, Kari E., Ingelsson, Erik, Hirschhorn, Joel N., Loos, Ruth J. F., Speliotes, Elizabeth K., Locke, Adam E., Kahali, Bratati, Berndt, Sonja I., Justice, Anne E., Pers, Tune H., Day, Felix R., Powell, Corey, Vedantam, Sailaja, Buchkovich, Martin L., Yang, Jian, Croteau-Chonka, Damien C., Esko, Tonu, Fall, Tove, Ferreira, Teresa, Gustafsson, Stefan, Kutalik, Zoltan, Luan, Jian'an, Maegi, Reedik, Randall, Joshua C., Winkler, Thomas W., Wood, Andrew R., Workalemahu, Tsegaselassie, Faul, Jessica D., Smith, Jennifer A., Zhao, Jing Hua, Zhao, Wei, Chen, Jin, Fehrmann, Rudolf, Hedman, Asa K., Karjalainen, Juha, Schmidt, Ellen M., Absher, Devin, Amin, Najaf, Anderson, Denise, Beekman, Marian, Bolton, Jennifer L., Bragg-Gresham, L., Buyske, Steven, Demirkan, Ayse, Deng, Guohong, Ehret, Georg B., Feenstra, Bjarke, Feitosa, Mary F., Fischer, Krista, Goel, Anuj, Gong, Jian, Jackson, Anne U., Kanoni, Stavroula, Kleber, Marcus E., Kristiansson, Kati, Lim, Unhee, Lotay, Vaneet, Mangino, Massimo, Leach, Irene Mateo, Medina-Gomez, Carolina, Medland, Sarah E., Nalls, Michael A., Palmer, Cameron D., Pasko, Dorota, Pechlivanis, Sonali, Peters, Marjolein J., Prokopenko, Inga, Shungin, Dmitry, Stancakova, Alena, Strawbridge, Rona J., Sung, Yun Ju, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, van der Laan, Sander W., van Settee, Jessica, Van Vliet-Ostaptchouk, Jana V., Wang, Zhaoming, Yengo, Loic, Zhang, Weihua, Isaacs, Aaron, Albrecht, Eva, Arnlov, Johan, Arscott, Gillian M., Attwood, Antony P., Bandinelli, Stefania, Barrett, Amy, Bas, Isabelita N., Bellis, Claire, Bennett, Amanda J., Berne, Christian, Blagieva, Roza, Blueher, Matthias, Bohringer, Stefan, Bonnycastle, Lori L., Boettcher, Yvonne, Boyd, Heather A., Bruinenberg, Marcel, Caspersen, Ida H., Chen, Yii-Der Ida, Clarke, Robert, Daw, E. Warwick, de Craen, Anton J. M., Delgado, Graciela, Dimitriou, Maria, Doney, Alex S. F., Eklund, Niina, Estrada, Karol, Eury, Elodie, Folkersen, Lasse, Fraser, Ross M., Garcia, Melissa E., Geller, Frank, Giedraitis, Vilmantas, Gigante, Bruna, Go, Alan S., Golay, Alain, Goodall, Alison H., Gordon, Scott D., Gorski, Mathias, Grabe, Hans-Joergen, Grallert, Harald, Grammer, Tanja B., Graessler, Jurgen, Gronberg, Henrik, Groves, Christopher J., Gusto, Gaeelle, Haessler, Jeffrey, Hall, Per, Haller, Toomas, Hallmans, Göran, Hartman, Catharina A., Hassinen, Maija, Hayward, Caroline, Heard-Costa, Nancy L., Helmer, Qinta, Hengstenberg, Christian, Holmen, Oddgeir, Hottenga, Jouke-Jan, James, Alan L., Jeff, Janina M., Johansson, Asa, Jolley, Jennifer, Juliusdottir, Thorhildur, Kinnunen, Leena, Koenig, Wolfgang, Koskenvuo, Markku, Kratzer, Wolfgang, Laitinen, Jaana, Lamina, Claudia, Leander, Karin, Lee, Nanette R., Lichtner, Peter, Lind, Lars, Lindstrom, Jaana, Lo, Ken Sin, Lobbens, Stephane, Lorbeer, Roberto, Lu, Yingchang, Mach, Francois, Magnusson, Patrik K. E., Mahajan, Anubha, McArdle, Wendy L., McLachlan, Stela, Menni, Cristina, Merger, Sigrun, Mihailov, Evelin, Milani, Lili, Moayyeri, Alireza, Monda, Keri L., Morken, Mario A., Mulas, Antonella, Mueller, Gabriele, Mueller-Nurasyid, Martina, Musk, Arthur W., Nagaraja, Ramaiah, Noethen, Markus M., Nolte, Ilja M., Pilz, Stefan, Rayner, Nigel W., Renstrom, Frida, Rettig, Rainer, Ried, Janina S., Ripke, Stephan, Robertson, Neil R., Rose, Lynda M., Sanna, Serena, Scharnagl, Hubert, Scholtens, Salome, Schumacher, Fredrick R., Scott, William R., Seufferlein, Thomas, Shi, Jianxin, Smith, Albert Vernon, Smolonska, Joanna, Stanton, Alice V., Steinthorsdottir, Valgerdur, Stirrups, Kathleen, Stringham, Heather M., Sundstrom, Johan, Swertz, Morris A., Swift, Amy J., Syvanen, Ann-Christine, Tan, Sian-Tsung, Tayo, Bamidele O., Thorand, Barbara, Thorleifsson, Gudmar, Tyrer, Jonathan P., Uh, Hae-Won, Vandenput, Liesbeth, Verhulst, Frank C., Vermeulen, Sita H., Verweij, Niek, Vonk, Judith M., Waite, Lindsay L., Warren, Helen R., Waterworth, Dawn, Weedon, Michael N., Wilkens, Lynne R., Willenborg, Christina, Wilsgaard, Tom, Wojczynski, Mary K., Wong, Andrew, Wrightl, Alan F., Zhang, Qunyuan, Brennan, Eoin P., Choi, Murim, Dastani, Zari, Drong, Alexander W., Eriksson, Per, Franco-Cereceda, Anders, Gadin, Jesper R., Gharavi, Ali G., Goddard, Michael E., Handsaker, Robert E., Huang, Jinyan, Karpe, Fredrik, Kathiresan, Sekar, Keildson, Sarah, Kiryluk, Krzysztof, Kubo, Michiaki, Lee, Jong-Young, Liang, Liming, Lifton, Richard P., Ma, Baoshan, McCarroll, Steven A., McKnight, Amy J., Min, Josine L., Moffatt, Miriam F., Montgomery, Grant W., Murabito, Joanne M., Nicholson, George, Nyholt, Dale R., Okada, Yukinori, Perry, John R. B., Dorajoo, Rajkumar, Reinmaa, Eva, Salem, Rany M., Sandholm, Niina, Scott, Robert A., Stolk, Lisette, Takahashi, Atsushi, Tanaka, Toshihiro, van 't Hooft, Ferdinand M., Vinkhuyzen, Anna A. E., Westra, Harm-Jan, Zheng, Wei, Zondervan, Krina T., Heath, Andrew C., Arveiler, Dominique, Bakker, Stephan J. L., Beilby, John, Bergman, Richard N., Blangero, John, Bovet, Pascal, Campbell, Harry, Caulfield, Mark J., Cesana, Giancarlo, Chakravarti, Aravinda, Chasman, Daniel I., Chines, Peter S., Collins, Francis S., Crawford, Dana C., Cupples, L. Adrienne, Cusi, Daniele, Danesh, John, de Faire, Ulf, den Ruijter, Hester M., Dominiczak, Anna F., Erbel, Raimund, Erdmann, Jeanette, Eriksson, Johan G., Farrall, Martin, Felix, Stephan B., Ferrannini, Ele, Ferrieres, Jean, Ford, Ian, Forouhi, Nita G., Forrester, Terrence, Franco, Oscar H., Gansevoort, Ron T., Gejman, Pablo V., Gieger, Christian, Gottesman, Omri, Gudnason, Vilmundur, Gyllensten, Ulf, Hall, Alistair S., Harris, Tamara B., Hattersley, Andrew T., Hicks, Andrew A., Hindorff, Lucia A., Hingorani, Aroon D., Hofman, Albert, Homuth, Georg, Hovingh, G. Kees, Humphries, Steve E., Hunt, Steven C., Hypponen, Elina, Illig, Thomas, Jacobs, Kevin B., Jarvelin, Marjo-Riitta, Joeckel, Karl-Heinz, Johansen, Berit, Jousilahti, Pekka, Jukema, J. Wouter, Jula, Antti M., Kaprio, Jaakko, Kastelein, John J. P., Keinanen-Kiukaanniemi, Sirkka M., Kiemeney, Lambertus A., Knekt, Paul, Kooner, Jaspal S., Kooperberg, Charles, Kovacs, Peter, Kraja, Aldi T., Kumari, Meena, Kuusisto, Johanna, Lakka, Timo A., Langenberg, Claudia, Le Marchand, Laic, Lehtimaki, Terho, Lyssenko, Valeriya, Mannisto, Satu, Marette, Andre, Matise, Tara C., McKenzie, Colin A., McKnight, Barbara, Moll, Frans L., Morris, Andrew D., Morris, Andrew P., Murray, Jeffrey C., Nelis, Mari, Ohlsson, Claes, Oldehinkel, Albertine J., Ong, Ken K., Madden, Pamela A. F., Pasterkamp, Gerard, Peden, John F., Peters, Annette, Postma, Dirkje S., Pramstaller, Peter P., Price, Jackie F., Qi, Lu, Raitakari, Olli T., Rankinen, Tuomo, Rao, D. C., Rice, Treva K., Ridker, Paul M., Rioux, John D., Ritchie, Marylyn D., Rudan, Igor, Salomaa, Veikko, Samani, Nilesh J., Saramines, Jouko, Sarzynski, Mark A., Schunkert, Heribert, Schwarz, Peter E. H., Sever, Peter, Shuldiner, Alan R., Sinisalo, Juha, Stolk, Ronald P., Strauch, Konstantin, Toenjes, Anke, Tregouet, David-Alexandre, Tremblay, Angelo, Tremoli, Elena, Virtamo, Jarmo, Vohl, Marie-Claude, Voelker, Uwe, Waeber, Gerard, Willemsen, Gonneke, Witteman, Jacqueline C., Zillikens, M. Carola, Adair, Linda S., Amouyel, Philippe, Asselbergs, Folkert W., Assimes, Themistocles L., Bochud, Murielle, Boehm, Bernhard O., Boerwinkle, Eric, Bornstein, Stefan R., Bottinger, Erwin P., Bouchard, Claude, Cauchi, Stephane, Chambers, John C., Chanock, Stephen J., Cooper, Richard S., de Bakker, Paul I. W., Dedoussis, George, Ferrucci, Luigi, Franks, Paul W., Froguel, Philippe, Groop, Leif C., Haiman, Christopher A., Hamsten, Anders, Hui, Jennie, Hunter, David J., Hveem, Kristian, Kaplan, Robert C., Kivimaki, Mika, Kuh, Diana, Laakso, Markku, Liu, Yongmei, Martin, Nicholas G., Maerz, Winfried, Melbve, Mads, Metspalu, Andres, Moebus, Susanne, Munroe, Patricia B., Njolstad, Inger, Oostra, Ben A., Palmer, Colin N. A., Pedersen, Nancy L., Perola, Markus, Perusse, Louis, Peters, Ulrike, Power, Chris, Quertermous, Thomas, Rauramaa, Rainer, Rivadeneira, Fernando, Saaristo, Timo E., Saleheen, Danish, Sattar, Naveed, Schadt, Eric E., Schlessinger, David, Slagboom, P. Eline, Snieder, Harold, Spector, Tim D., Thorsteinsdottir, Unnu R., Stumvoll, Michael, Tuomilehto, Jaakko, Uitterlinden, Andre G., Uusitupa, Matti, van der Harst, Pim, Walker, Mark, Wallaschofski, Henri, Wareham, Nicholas J., Watkins, Hugh, Weir, David R., Wichmann, H-Erich, Wilson, James F., Zanen, Pieter, Borecki, Ingrid B., Deloukas, Panos, Fox, Caroline S., Heid, Iris M., O'Connell, Jeffrey R., Strachan, David P., Stefansson, Kari, van Duijri, Cornelia M., Abecasis, Goncalo R., Franke, Lude, Frayling, Timothy M., McCarthy, Mark I., Visscher, Peter M., Scherag, Andre, Willer, Cristen J., Boehnke, Michael, Mohlke, Karen L., Lindgren, Cecilia M., Beckmann, Jacques S., Barroso, Ines, North, Kari E., Ingelsson, Erik, Hirschhorn, Joel N., Loos, Ruth J. F., and Speliotes, Elizabeth K.

Abstract

Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in upto 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 x 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for similar to 2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous systemin obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.

Published
2015
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158. New genetic loci link adipose and insulin biology to body fat distribution

Author

Shungin, Dmitry, Winkler, Thomas W., Croteau-Chonka, Damien C., Ferreira, Teresa, Lockes, Adam E., Maegi, Reedik, Strawbridge, Rona J., Pers, Tune H., Fischer, Krista, Justice, Anne E., Workalemahu, Tsegaselassie, Wu, Joseph M. W., Buchkovich, Martin L., Heard-Costa, Nancy L., Roman, Tamara S., Drong, Alexander W., Song, Ci, Gustafsson, Stefan, Day, Felix R., Esko, Tonu, Fall, Tove, Kutalik, Zoltan, Luan, Jian'an, Randall, Joshua C., Scherag, Andre, Vedantam, Sailaja, Wood, Andrew R., Chen, Jin, Fehrmann, Rudolf, Karjalainen, Juha, Kahali, Bratati, Liu, Ching-Ti, Schmidt, Ellen M., Absher, Devin, Amin, Najaf, Anderson, Denise, Beekman, Marian, Bragg-Gresham, Jennifer L., Buyske, Steven, Demirkan, Ayse, Ehret, Georg B., Feitosa, Mary F., Goel, Anuj, Jackson, Anne U., Johnson, Toby, Kleber, Marcus E., Kristiansson, Kati, Mangino, Massimo, Leach, Irene Mateo, Medina-Gomez, Carolina, Palmer, Cameron D., Pasko, Dorota, Pechlivaniss, Sonali, Peters, Marjolein J., Prokopenko, Inga, Stancakova, Alena, Sung, Yun Ju, Tanakam, Toshiko, Teumer, Alexander, Van Vliet-Ostaptchouk, Jana V., Yengo, Loic, Zhang, Weihua, Albrecht, Eva, Arnlov, Johan, Arscott, Gillian M., Bandinelli, Stefania, Barrett, Amy, Bellis, Claire, Bennett, Amanda J., Berne, Christian, Blueher, Matthias, Buhringer, Stefan, Bonnet, Fabrice, Boettcher, Yvonne, Bruinenberg, Marcel, Carba, Delia B., Caspersen, Ida H., Clarke, Robert, Daw, E. Warwick, Deelen, Joris, Deelman, Ewa, Delgado, Graciela, Doney, Alex S. F., Eklund, Niina, Erdos, Michael R., Estrada, Karol, Eury, Elodie, Friedrichs, Nele, Garcia, Melissa E., Giedraitis, Vilmantas, Gigante, Bruna, Go, Alan S., Golay, Alain, Grallert, Harald, Grammer, Tanja B., Graessler, Juergen, Grewal, Jagvir, Groves, Christopher J., Haller, Toomas, Hallmans, Göran, Hartman, Catharina A., Hassinen, Maija, Hayward, Caroline, Heikkila, Kauko, Herzig, Karl-Heinz, Helmer, Quinta, Hillege, Hans L., Holmen, Oddgeir, Hunt, Steven C., Isaacs, Aaron, Ittermann, Till, James, Alan L., Johansson, Ingegerd, Juliusdottir, Thorhildur, Kalafati, Ioanna-Panagiota, Kinnunen, Leena, Koenig, Wolfgang, Kooner, Ishminder K., Kratzer, Wolfgang, Lamina, Claudia, Leander, Karin, Lee, Nanette R., Lichtner, Peter, Lind, Lars, Lindstrom, Jaana, Lobbens, Stephane, Lorentzon, Mattias, Mach, Francois, Magnusson, Patrik K. E., Mahajan, Anubha, McArdle, Wendy L., Menni, Cristina, Merger, Sigrun, Mihailov, Evelin, Milani, Lili, Mills, Rebecca, Moayyeri, Alireza, Monda, Ken L., Mooijaart, Simon P., Muehleisen, Thomas W., Mulas, Antonella, Mueller, Gabriele, Mueller-Nurasyid, Martina, Nagaraja, Ramaiah, Nalls, Michael A., Narisu, Narisu, Glorioso, Nicola, Nolte, Ilja M., Olden, Matthias, Rayner, Nigel W., Renstrom, Frida, Ried, Janina S., Robertson, Neil R., Rose, Lynda M., Sanna, Serena, Scharnagl, Hubert, Scholtens, Salome, Sennblad, Bengt, Seufferlein, Thomas, Sitlani, Colleen M., Smith, Albert Vernon, Stirrups, Kathleen, Stringham, Heather M., Sundstrom, Johan, Swertz, Morris A., Swift, Amy J., Syvanen, Ann-Christine, Tayo, Bamidele O., Thorand, Barbara, Thorleifsson, Gudmar, Tomaschitz, Andreas, Troffa, Chiara, van Oort, Floor V. A., Verweij, Niek, Vonk, Judith M., Waite, Lindsay L., Wennauer, Roman, Wilsgaard, Tom, Wojczynski, Mary K., Wong, Andrew, Zhang, Qunyuan, Zhao, Jing Hua, Brennan, Eoin P., Choi, Murim, Eriksson, Per, Folkersen, Lasse, Franco-Cereceda, Anders, Gharavi, Ali G., Hedman, Asa K., Hivert, Marie-France, Huang, Jinyan, Kanoni, Stavroula, Karpe, Fredrik, Keildson, Sarah, Kiryluk, Krzysztof, Liang, Liming, Lifton, Richard P., Ma, Baoshan, McKnight, Amy J., McPherson, Ruth, Metspalu, Andres, Min, Josine L., Moffatt, Miriam F., Montgomery, Grant W., Murabito, Joanne M., Nicholson, George, Nyholt, Dale R., Olsson, Christian, Perry, John R. B., Reinmaa, Eva, Salem, Rany M., Sandholm, Niina, Schadt, Eric E., Scott, Robert A., Stolk, Lisette, Vallejo, Edgar E., Westra, Harm-Jan, Zondervan, Krina T., Amouyel, Philippe, Arveiler, Dominique, Bakker, Stephan J. L., Beilby, John, Bergman, Richard N., Blangero, John, Brown, Morris J., Burnier, Michel, Campbell, Harry, Chakravarti, Aravinda, Chiness, Peter S., Claudi-Boehmi, Simone, Collins, Francis S., Crawford, Dana C., Danesh, John, de Faire, Ulf, de Geusl, Eco J. C., Doerr, Marcus, Erbel, Raimund, Eriksson, Johan G., Farrall, Martin, Ferrannini, Ele, Ferrieres, Jean, Forouhi, Nita G., Forrester, Terrence, Franco, Oscar H., Gansevoort, Ron T., Gieger, Christian, Gudnason, Vilmundur, Haiman, Christopher A., Harris, Tamara B., Hattersley, Andrew T., Heliovaara, Markku, Hicks, Andrew A., Hingorani, Aroon D., Hoffmann, Wolfgang, Hofman, Albert, Homuth, Georg, Humphries, Steve E., Hyppoenen, Elina, Illig, Thomas, Jarvelin, Marjo-Riitta, Johansen, Berit, Jousilahti, Pekka, Jula, Antti M., Kaprio, Jaakko, Kee, Frank, Keinanen-Kiukaanniemi, Sirkka M., Kooner, Jaspal S., Kooperberg, Charles, Kovacs, Peter, Kraja, Aldi T., Kumari, Meena, Kuulasmaa, Kari, Kuusisto, Johanna, Lakka, Timo A., Langenberg, Claudia, Le Marchand, Loic, Lehtimaki, Terho, Lyssenko, Valeriya, Mannisto, Satu, Marette, Andre, Matise, Tara C., McKenzie, Colin A., McKnight, Barbara, Musk, Arthur W., Mohlenkamp, Stefan, Morris, Andrew D., Nelis, Mari, Ohlsson, Claes, Oldehinkel, Albertine J., Ong, Ken K., Palmer, Lyle J., Penninx, Brenda W., Peters, Annette, Pramstaller, Peter P., Raitakari, Olli T., Rankinen, Tuomo, Rao, D. C., Rice, Treva K., Ridker, Paul M., Ritchie, Marylyn D., Rudan, Igor, Salomaa, Veikko, Samani, Nilesh J., Saramies, Jouko, Sarzynski, Mark A., Schwarz, Peter E. H., Shuldiner, Alan R., Staessen, Jan A., Steinthorsdottir, Valgerdur, Stolk, Ronald P., Strauch, Konstantin, Toenjes, Anke, Tremblay, Angelo, Tremoli, Elena, Vohl, Marie-Claude, Voelker, Uwe, Vollenweider, Peter, Wilson, James F., Witteman, Jacqueline C., Adair, Linda S., Bochud, Murielle, Boehm, Bernhard O., Bornstein, Stefan R., Bouchard, Claude, Cauchi, Stephane, Caulfield, Mark J., Chambers, John C., Chasman, Daniel I., Cooper, Richard S., Dedoussis, George, Ferrucci, Luigi, Froguel, Philippe, Grabe, Hans-Joergen, Hamsten, Anders, Hui, Jennie, Hveem, Kristian, Joeckel, Karl-Heinz, Kivimaki, Mika, Kuh, Diana, Laakso, Markku, Liu, Yongmei, Maerz, Winfried, Munroe, Patricia B., Njolstad, Inger, Oostra, Ben A., Palmer, Colin N. A., Pedersen, Nancy L., Perola, Markus, Perusse, Louis, Peters, Ulrike, Power, Chris, Quertermous, Thomas, Rauramaa, Rainer, Rivadeneira, Fernando, Saaristo, Timo E., Saleheen, Danish, Sinisalo, Juha, Slagboom, P. Eline, Snieder, Harold, Spector, Tim D., Thorsteinsdottir, Unnur R., Stumvoll, Michael, Tuomilehto, Jaakko, Uitterlinden, Andre G., Uusitupa, Math, van der Harst, Pim, Veronesi, Giovanni, Walker, Mark, Wareham, Nicholas J., Watkins, Hugh, Wichmann, H-Erich, Abecasis, Goncalo R., Assimes, Themistocles L., Berndt, Sonja I., Boehnkes, Michael, Borecki, Ingrid B., Deloukas, Panos, Franke, Lude, Frayling, Timothy M., Groop, Leif C., Hunter, David J., Kaplan, Robert C., O'Connell, Jeffrey R., Qi, Lu, Schlessinger, David, Strachan, David P., Stefansson, Kari, van Dujin, Cornelia M., Willer, Cristen J., Visscher, Peter M., Yang, Jian, Hirschhorn, Joel N., Zillikens, M. Carola, McCarthy, Mark I., Speliotes, Elizabeth K., North, Kari E., Fox, Caroline S., Barroso, Ines, Franks, Paul W., Ingelsson, Erik, Heid, Iris M., Loos, Ruth J. F., Cupples, L. Adrienne, Morris, Andrew P., Lindgren, Cecilia M., Mohlke, Karen L., Shungin, Dmitry, Winkler, Thomas W., Croteau-Chonka, Damien C., Ferreira, Teresa, Lockes, Adam E., Maegi, Reedik, Strawbridge, Rona J., Pers, Tune H., Fischer, Krista, Justice, Anne E., Workalemahu, Tsegaselassie, Wu, Joseph M. W., Buchkovich, Martin L., Heard-Costa, Nancy L., Roman, Tamara S., Drong, Alexander W., Song, Ci, Gustafsson, Stefan, Day, Felix R., Esko, Tonu, Fall, Tove, Kutalik, Zoltan, Luan, Jian'an, Randall, Joshua C., Scherag, Andre, Vedantam, Sailaja, Wood, Andrew R., Chen, Jin, Fehrmann, Rudolf, Karjalainen, Juha, Kahali, Bratati, Liu, Ching-Ti, Schmidt, Ellen M., Absher, Devin, Amin, Najaf, Anderson, Denise, Beekman, Marian, Bragg-Gresham, Jennifer L., Buyske, Steven, Demirkan, Ayse, Ehret, Georg B., Feitosa, Mary F., Goel, Anuj, Jackson, Anne U., Johnson, Toby, Kleber, Marcus E., Kristiansson, Kati, Mangino, Massimo, Leach, Irene Mateo, Medina-Gomez, Carolina, Palmer, Cameron D., Pasko, Dorota, Pechlivaniss, Sonali, Peters, Marjolein J., Prokopenko, Inga, Stancakova, Alena, Sung, Yun Ju, Tanakam, Toshiko, Teumer, Alexander, Van Vliet-Ostaptchouk, Jana V., Yengo, Loic, Zhang, Weihua, Albrecht, Eva, Arnlov, Johan, Arscott, Gillian M., Bandinelli, Stefania, Barrett, Amy, Bellis, Claire, Bennett, Amanda J., Berne, Christian, Blueher, Matthias, Buhringer, Stefan, Bonnet, Fabrice, Boettcher, Yvonne, Bruinenberg, Marcel, Carba, Delia B., Caspersen, Ida H., Clarke, Robert, Daw, E. Warwick, Deelen, Joris, Deelman, Ewa, Delgado, Graciela, Doney, Alex S. F., Eklund, Niina, Erdos, Michael R., Estrada, Karol, Eury, Elodie, Friedrichs, Nele, Garcia, Melissa E., Giedraitis, Vilmantas, Gigante, Bruna, Go, Alan S., Golay, Alain, Grallert, Harald, Grammer, Tanja B., Graessler, Juergen, Grewal, Jagvir, Groves, Christopher J., Haller, Toomas, Hallmans, Göran, Hartman, Catharina A., Hassinen, Maija, Hayward, Caroline, Heikkila, Kauko, Herzig, Karl-Heinz, Helmer, Quinta, Hillege, Hans L., Holmen, Oddgeir, Hunt, Steven C., Isaacs, Aaron, Ittermann, Till, James, Alan L., Johansson, Ingegerd, Juliusdottir, Thorhildur, Kalafati, Ioanna-Panagiota, Kinnunen, Leena, Koenig, Wolfgang, Kooner, Ishminder K., Kratzer, Wolfgang, Lamina, Claudia, Leander, Karin, Lee, Nanette R., Lichtner, Peter, Lind, Lars, Lindstrom, Jaana, Lobbens, Stephane, Lorentzon, Mattias, Mach, Francois, Magnusson, Patrik K. E., Mahajan, Anubha, McArdle, Wendy L., Menni, Cristina, Merger, Sigrun, Mihailov, Evelin, Milani, Lili, Mills, Rebecca, Moayyeri, Alireza, Monda, Ken L., Mooijaart, Simon P., Muehleisen, Thomas W., Mulas, Antonella, Mueller, Gabriele, Mueller-Nurasyid, Martina, Nagaraja, Ramaiah, Nalls, Michael A., Narisu, Narisu, Glorioso, Nicola, Nolte, Ilja M., Olden, Matthias, Rayner, Nigel W., Renstrom, Frida, Ried, Janina S., Robertson, Neil R., Rose, Lynda M., Sanna, Serena, Scharnagl, Hubert, Scholtens, Salome, Sennblad, Bengt, Seufferlein, Thomas, Sitlani, Colleen M., Smith, Albert Vernon, Stirrups, Kathleen, Stringham, Heather M., Sundstrom, Johan, Swertz, Morris A., Swift, Amy J., Syvanen, Ann-Christine, Tayo, Bamidele O., Thorand, Barbara, Thorleifsson, Gudmar, Tomaschitz, Andreas, Troffa, Chiara, van Oort, Floor V. A., Verweij, Niek, Vonk, Judith M., Waite, Lindsay L., Wennauer, Roman, Wilsgaard, Tom, Wojczynski, Mary K., Wong, Andrew, Zhang, Qunyuan, Zhao, Jing Hua, Brennan, Eoin P., Choi, Murim, Eriksson, Per, Folkersen, Lasse, Franco-Cereceda, Anders, Gharavi, Ali G., Hedman, Asa K., Hivert, Marie-France, Huang, Jinyan, Kanoni, Stavroula, Karpe, Fredrik, Keildson, Sarah, Kiryluk, Krzysztof, Liang, Liming, Lifton, Richard P., Ma, Baoshan, McKnight, Amy J., McPherson, Ruth, Metspalu, Andres, Min, Josine L., Moffatt, Miriam F., Montgomery, Grant W., Murabito, Joanne M., Nicholson, George, Nyholt, Dale R., Olsson, Christian, Perry, John R. B., Reinmaa, Eva, Salem, Rany M., Sandholm, Niina, Schadt, Eric E., Scott, Robert A., Stolk, Lisette, Vallejo, Edgar E., Westra, Harm-Jan, Zondervan, Krina T., Amouyel, Philippe, Arveiler, Dominique, Bakker, Stephan J. L., Beilby, John, Bergman, Richard N., Blangero, John, Brown, Morris J., Burnier, Michel, Campbell, Harry, Chakravarti, Aravinda, Chiness, Peter S., Claudi-Boehmi, Simone, Collins, Francis S., Crawford, Dana C., Danesh, John, de Faire, Ulf, de Geusl, Eco J. C., Doerr, Marcus, Erbel, Raimund, Eriksson, Johan G., Farrall, Martin, Ferrannini, Ele, Ferrieres, Jean, Forouhi, Nita G., Forrester, Terrence, Franco, Oscar H., Gansevoort, Ron T., Gieger, Christian, Gudnason, Vilmundur, Haiman, Christopher A., Harris, Tamara B., Hattersley, Andrew T., Heliovaara, Markku, Hicks, Andrew A., Hingorani, Aroon D., Hoffmann, Wolfgang, Hofman, Albert, Homuth, Georg, Humphries, Steve E., Hyppoenen, Elina, Illig, Thomas, Jarvelin, Marjo-Riitta, Johansen, Berit, Jousilahti, Pekka, Jula, Antti M., Kaprio, Jaakko, Kee, Frank, Keinanen-Kiukaanniemi, Sirkka M., Kooner, Jaspal S., Kooperberg, Charles, Kovacs, Peter, Kraja, Aldi T., Kumari, Meena, Kuulasmaa, Kari, Kuusisto, Johanna, Lakka, Timo A., Langenberg, Claudia, Le Marchand, Loic, Lehtimaki, Terho, Lyssenko, Valeriya, Mannisto, Satu, Marette, Andre, Matise, Tara C., McKenzie, Colin A., McKnight, Barbara, Musk, Arthur W., Mohlenkamp, Stefan, Morris, Andrew D., Nelis, Mari, Ohlsson, Claes, Oldehinkel, Albertine J., Ong, Ken K., Palmer, Lyle J., Penninx, Brenda W., Peters, Annette, Pramstaller, Peter P., Raitakari, Olli T., Rankinen, Tuomo, Rao, D. C., Rice, Treva K., Ridker, Paul M., Ritchie, Marylyn D., Rudan, Igor, Salomaa, Veikko, Samani, Nilesh J., Saramies, Jouko, Sarzynski, Mark A., Schwarz, Peter E. H., Shuldiner, Alan R., Staessen, Jan A., Steinthorsdottir, Valgerdur, Stolk, Ronald P., Strauch, Konstantin, Toenjes, Anke, Tremblay, Angelo, Tremoli, Elena, Vohl, Marie-Claude, Voelker, Uwe, Vollenweider, Peter, Wilson, James F., Witteman, Jacqueline C., Adair, Linda S., Bochud, Murielle, Boehm, Bernhard O., Bornstein, Stefan R., Bouchard, Claude, Cauchi, Stephane, Caulfield, Mark J., Chambers, John C., Chasman, Daniel I., Cooper, Richard S., Dedoussis, George, Ferrucci, Luigi, Froguel, Philippe, Grabe, Hans-Joergen, Hamsten, Anders, Hui, Jennie, Hveem, Kristian, Joeckel, Karl-Heinz, Kivimaki, Mika, Kuh, Diana, Laakso, Markku, Liu, Yongmei, Maerz, Winfried, Munroe, Patricia B., Njolstad, Inger, Oostra, Ben A., Palmer, Colin N. A., Pedersen, Nancy L., Perola, Markus, Perusse, Louis, Peters, Ulrike, Power, Chris, Quertermous, Thomas, Rauramaa, Rainer, Rivadeneira, Fernando, Saaristo, Timo E., Saleheen, Danish, Sinisalo, Juha, Slagboom, P. Eline, Snieder, Harold, Spector, Tim D., Thorsteinsdottir, Unnur R., Stumvoll, Michael, Tuomilehto, Jaakko, Uitterlinden, Andre G., Uusitupa, Math, van der Harst, Pim, Veronesi, Giovanni, Walker, Mark, Wareham, Nicholas J., Watkins, Hugh, Wichmann, H-Erich, Abecasis, Goncalo R., Assimes, Themistocles L., Berndt, Sonja I., Boehnkes, Michael, Borecki, Ingrid B., Deloukas, Panos, Franke, Lude, Frayling, Timothy M., Groop, Leif C., Hunter, David J., Kaplan, Robert C., O'Connell, Jeffrey R., Qi, Lu, Schlessinger, David, Strachan, David P., Stefansson, Kari, van Dujin, Cornelia M., Willer, Cristen J., Visscher, Peter M., Yang, Jian, Hirschhorn, Joel N., Zillikens, M. Carola, McCarthy, Mark I., Speliotes, Elizabeth K., North, Kari E., Fox, Caroline S., Barroso, Ines, Franks, Paul W., Ingelsson, Erik, Heid, Iris M., Loos, Ruth J. F., Cupples, L. Adrienne, Morris, Andrew P., Lindgren, Cecilia M., and Mohlke, Karen L.

Abstract

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 x 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

Published
2015
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160. Dietary Fish Protein Prevents Skeletal Muscle Insulin Resistance in Rats Fed a High-Fat Diet

Author

LAVIGNE, CHARLES, JACQUES, HELENE, TREMBLAY, FREDERIC, ASSELIN, GENEVIEVE, and MARETTE, ANDRE

Subjects
Diabetes -- Research, Health
Abstract

Previous studies have shown that rats fed a saturated high-fat diet develop peripheral insulin resistance. The role of dietary proteins in the development of insulin resistance has not yet been [...]

Published
1999

167. List of Contributors

Author

Akabanda, Fortune, Altay, Filiz, Antunes, Adriane E.C., Arendt, Elke, Aryana, Kayanush J., Athira, Syamala, Bajaj, Rajesh, Bianchi, Fernanda, Biver, Emmanuel, Bogsan, Cristina S.B., Busetti, Francesco, Buyuktuncer, Zehra, Chandan, Ramesh C., Cliff, Margaret, Coda, Rossana, Cortez, Marco Antônio S., Cruz, Adriano G., Danova, Svetla, Dugan, Christine E., Esmerino, Erick A., Fan, Lihua, Fernandez, Maria Luz, Fernandez, Melissa A., Fisberg, Mauro, Freire, Fernanda C., Gandhi, Akanksha, Gawai, Kunal M., Hemsworth, Jaimie, Hernández-Borges, Javier, Herrera-Herrera, Antonio V., Hill, Daragh, Hummelen, Ruben, Huppertz, Thom, Jespersen, Lene, Johansen, Pernille, Kilara, Arun, Lima, Ana Carolina D., Lopes, Natalia P., Magiatis, Prokopios, Mann, Bimlesh, Marette, André, Melliou, Eleni, Moatsou, Golfo, Montemurro, Marco, Morelli, Lorenzo, Mudgal, Sreeja P., Nemska, Veronica, Nguyen, Doan D., Nielsen, Dennis S., Oliveira, Maricê N., Olson, Douglas, Owusu-Kwarteng, James, Pimentel, Tatiana C., Pires, Ana Carolina M.S., Prajapati, Jashbhai B., H.P. Prasanna, Pradeep, Rabbani Khorasgani, Mohammad, Rastall, Robert A., Rizzello, Carlo G., Rizzoli, René, Rodríguez-Delgado, Miguel Ángel, Ross, Reynolds P., Roy, Denis, Settachaimongkon, Sarn, Sgarbosa, Letícia, Shafiei, Rasoul, Shah, Nagendra P., Sharma, Rajan, Shiraishi, Christiane T.D., Silva, Marcia C., Singh, Pranav K., Sivieri, Katia, Smid, Eddy J., Socas-Rodríguez, Bárbara, Solah, Vicky A., Stanton, Catherine, Tropcheva, Rositsa, van Valenberg, Hein J.F., Zacarchenco, Patrícia B., Zavarizi, Adriana C.M., and Zoidou, Evangelia

Published
2017
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175. Contributors

Author

Baldi, Antonella, Bath, Sarah C., Breen, Leigh, Butler, Gillian, Cooper, Lydia, Dawczynski, Christine, Dougkas, Anestis, Feeney, Emma L., Fekete, Ágnes A., Fernandez, Melissa Anne, Giromini, Carlotta, Givens, D. Ian, Gunn, Caroline, Guo, Jing, Hill, Tom R., Hocking, Erica, Iuliano, Sandra, Jahreis, Gerhard, Kliem, Kirsty E., Lovegrove, Julie A., Marette, André, Markey, Oonagh, McKinley, Michelle C., Miles, Elizabeth A., Pinotti, Luciano, Rayman, Margaret P., Smeuninx, Benoit, Soedamah-Muthu, Sabita S., Stergiadis, Sokratis, and Walsh, Marianne C.

Published
2020
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181. Prevention of oxidative stress, inflammation and mitochondrial dysfunction in the intestine by different cranberry phenolic fractions.

Author

Denis, Marie-Claude, Desjardin, Yves, Furtos, Alexandra, Marcil, Valérie, Dudonné, Stéphanie, Montoudis, Alain, Garofalo, Carole, Delvin, Edgard, Marette, Andre, and Lev, Emile

Subjects
INFLAMMATORY bowel diseases, OXIDATIVE stress, MITOCHONDRIAL pathology, CRANBERRIES, POLYPHENOLS, ANTIOXIDANTS, PREVENTION
Abstract

Cranberry fruit has been reported to have high antioxidant effectiveness that is potentially linked to its richness in diversified polyphenolic content. The aim of the present study was to determine the role of cranberry polyphenolic fractions in oxidative stress (OxS), inflammation and mitochondrial functions using intestinal Caco-2/15 cells. The combination of HPLC and UltraPerformance LC®-tandem quadrupole (UPLC-TQD) techniques allowed us to characterize the profile of low, medium and high molecular mass polyphenolic compounds in cranberry extracts. The medium molecular mass fraction was enriched with flavonoids and procyanidin dimers whereas procyanidin oligomers (DP > 4) were the dominant class of polyphenols in the high molecular mass fraction. Pre-incubation of Caco-2/15 cells with these cranberry extracts prevented iron/ascorbate-mediated lipid peroxidation and counteracted lipopolysaccharide-mediated inflammation as evidenced by the decrease in pro-inflammatory cytokines (TNF-a and interleukin-6), cyclo-oxygenase-2 and prostaglandin E2. Cranberry polyphenols (CP) fractions limited both nuclear factor KB activation and Nrf2 down-regulation. Consistently, cranberry procyanidins alleviated OxS-dependent mitochondrial dysfunctions as shown by the rise in ATP production and the up-regulation of Bcl-2, as well as the decline of protein expression of cytochrome c and apoptotic-inducing factor. These mitochondrial effects were associated with a significant stimulation of peroxisome-proliferator-activated receptor y co-activator-1-a, a central inducing factor of mitochondrial biogenesis and transcriptional co-activator of numerous downstream mediators. Finally, cranberry procyanidins forestalled the effect of iron/ascorbate on the protein expression of mitochondrial transcription factors (mtTFA, mtTFB1, mtTFB2). Our findings provide evidence for the capacity of CP to reduce intestinal OxS and inflammation while improving mitochondrial dysfunction. [ABSTRACT FROM AUTHOR]

Published
2015
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188. Functional significance of skeletal muscle adiponectin production, changes in animal models of obesity and diabetes, and regulation by rosiglitazone treatment.

Author

Ying Liu, Chewchuk, Simon, Lavigne, Charles, Brûlé, Sophie, Pilon, Genevieve, Houde, Vanessa, Aimin Xu, Marette, Andre, and Sweeney, Gary

Subjects
PROTEINS, MUSCLES, LABORATORY rats, LABORATORY mice, OBESITY, DIABETES, ROSIGLITAZONE, INSULIN resistance
Abstract

Endocrine effects of adipose-derived adiponectin on skeletal muscle have been shown to account, at least in part, for the anti-diabetic effects of this adipokine. Recently, the concept of myokines has gained credence, and the potential for skeletal muscle to produce adiponectin has been suggested. Here we demonstrated an increased level of adiponectin mRNA and protein expression as well as protein secretion in response to rosiglitazone treatment in L6 muscle cells. This correlated with the ability of rosiglitazone to enhance insulin sensitivity for stimulation of protein kinase B (Akt) phosphorylation and glucose transport; rosiglitazone also corrected high-glucose-induced insulin resistance in L6 cells. Overexpression of adiponectin confirmed the functional significance of local production of adiponectin in muscle cells via elevated glucose uptake and increased insulin sensitivity. In obese diabetic db/db mice, there was a change in the adiponectin expression profile in soleus and extensor digitorum longus (EDL) muscle with less high molecular weight (HMW) and more medium (MMW)flow (LMW) molecular weight species detected. Induction of obesity and insulin resistance in rats by feeding a high-fat high-sucrose diet also led to decreased muscle HMW adiponectin content that could be corrected by rosiglitazone treatment. In summary, we show the ability of skeletal muscle cells to produce adiponectin, which can mediate autocrine metabolic effects, thus establishing adiponectin as a bona fide myokine. We also demonstrate that skeletal muscle adiponectin production is altered in animal models of obesity and diabetes and that these changes can be corrected by rosiglitazone. [ABSTRACT FROM AUTHOR]

Published
2009
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190. The AMP-activated protein kinase activator AICAR does not induce GLUT4 translocation to transverse tubules but stimulates glucose uptake and p38 mitogen-activated protein kinases α and Β...

Author

Lemieux, Kathleen, Konrad, Daniel, Klip, Amira, and Marette, Andre

Subjects
PROTEIN kinases, PHOSPHOTRANSFERASES, GLUCOSE, MUSCLES, MUSCLE contraction
Abstract

Investigates whether the AMP-activated protein kinase activator AICAR increases glucose uptake by inducing the translocation of GLUT4. Result that occurs from the contraction on muscle glucose uptake; Manner in which muscle contraction increases glucose uptake and utilization; Events that activate p38 MAPK in rat skeletal muscle.

Published
2003
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191. Induction of insulin resistance by high-sucrose feeding does not raise mean arterial blood pressure but impairs haemodynamic responses to insulin in rats.

Author

Santure, Marta, Pitre, Maryse, Marette, Andre, Deshaies, Yves, Lemieux, Christian, Lariviere, Richard, Nadeau, Andre, and Bachelard, Helene

Subjects
INSULIN resistance, RATS, BLOOD pressure, SUCROSE
Abstract

1 This study was undertaken to further investigate the effects of a sucrose-enriched diet on vascular function and insulin sensitivity in rats. 2 Male Sprague-Dawley rats were randomized to receive a sucrose- or regular rat chow-diet for 4 weeks. A first group of sucrose- and chow-fed rats was instrumented with pulsed Doppler flow probes and intravascular catheters to determine blood pressure, heart rate, regional blood flows and insulin sensitivity in conscious rats. Insulin sensitivity was assessed by the euglycemic hyperinsulinemic clamp technique. Glucose transport activity was examined in isolated muscles by using the glucose analogue [³H]-2-deoxy-D-glucose. A second group of sucrose- and chow-fed rats was used to obtain information regarding nitric oxide synthase (NOS) isozymes protein expression in muscles, and determine endothelin content in vascular tissues isolated from both dietary groups. 3 Sucrose feeding was found to induce insulin resistance, but had no effect on resting blood pressure, heart rate, or regional haemodynamics. This insulin resistance was accompanied by alteration in the vascular responses to insulin. Insulin-mediated skeletal muscle vasodilation was impaired, whereas the mesenteric vasoconstrictor response was potentiated in sucrose-fed rats. A reduction in eNOS protein content in muscle and an increase in vascular endothelin peptide were noted in these animals. Moreover, a reduction in insulin-simulated glucose transport activity was also noted in muscles isolated from sucrose-fed rats. 4 Together these data suggest that a cluster of metabolic and haemodynamic abnormalities occur in response to the intake of simple sugars in rats. [ABSTRACT FROM AUTHOR]

Published
2002
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192. Defective insulin-induced GLUT4 translocation in skeletal muscle of high fat-fed rats is associated with alterations in both Akt/protein kinase B and atypical protein kinase C (zeta/lambda) activities.

Author

Tremblay, Frederic, Lavigne, Charles, Jacques, Helene, Marette, Andre, Tremblay, F, Lavigne, C, Jacques, H, and Marette, A

Subjects
PROTEIN kinases, INSULIN resistance, LABORATORY rats
Abstract

The cellular mechanism by which high-fat feeding induces skeletal muscle insulin resistance was investigated in the present study. Insulin-stimulated glucose transport was impaired ( approximately 40-60%) in muscles of high fat-fed rats. Muscle GLUT4 expression was significantly lower in these animals ( approximately 40%, P < 0.05) but only in type IIa-enriched muscle. Insulin stimulated the translocation of GLUT4 to both the plasma membrane and the transverse (T)-tubules in chow-fed rats. In marked contrast, GLUT4 translocation was completely abrogated in the muscle of insulin-stimulated high fat-fed rats. High-fat feeding markedly decreased insulin receptor substrate (IRS)-1-associated phosphatidylinositol (PI) 3-kinase activity but not insulin-induced tyrosine phosphorylation of the insulin receptor and IRS proteins in muscle. Impairment of PI 3-kinase function was associated with defective Akt/protein kinase B kinase activity (-40%, P < 0.01) in insulin-stimulated muscle of high fat-fed rats, despite unaltered phosphorylation (Ser473/Thr308) of the enzyme. Interestingly, basal activity of atypical protein kinase C (aPKC) was elevated in muscle of high fat-fed rats compared with chow-fed controls. Whereas insulin induced a twofold increase in aPKC kinase activity in the muscle of chow-fed rats, the hormone failed to further increase the kinase activity in high fat-fed rat muscle. In conclusion, it was found that GLUT4 translocation to both the plasma membrane and the T-tubules is impaired in the muscle of high fat-fed rats. We identified PI 3-kinase as the first step of the insulin signaling pathway to be impaired by high-fat feeding, and this was associated with alterations in both Akt and aPKC kinase activities. [ABSTRACT FROM AUTHOR]

Published
2001
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193. New genetic loci link adipose and insulin biology to body fat distribution

Author

Shungin, Dmitry, Winkler, Thomas W, Croteau-Chonka, Damien C, Ferreira, Teresa, Locke, Adam E, Mägi, Reedik, Strawbridge, Rona J, Pers, Tune H, Fischer, Krista, Justice, Anne E, Workalemahu, Tsegaselassie, Wu, Joseph M.W., Buchkovich, Martin L, Heard-Costa, Nancy L, Roman, Tamara S, Drong, Alexander W, Song, Ci, Gustafsson, Stefan, Day, Felix R, Esko, Tonu, Fall, Tove, Kutalik, Zoltán, Luan, Jian’an, Randall, Joshua C, Scherag, André, Vedantam, Sailaja, Wood, Andrew R, Chen, Jin, Fehrmann, Rudolf, Karjalainen, Juha, Kahali, Bratati, Liu, Ching-Ti, Schmidt, Ellen M, Absher, Devin, Amin, Najaf, Anderson, Denise, Beekman, Marian, Bragg-Gresham, Jennifer L, Buyske, Steven, Demirkan, Ayse, Ehret, Georg B, Feitosa, Mary F, Goel, Anuj, Jackson, Anne U, Johnson, Toby, Kleber, Marcus E, Kristiansson, Kati, Mangino, Massimo, Leach, Irene Mateo, Medina-Gomez, Carolina, Palmer, Cameron D, Pasko, Dorota, Pechlivanis, Sonali, Peters, Marjolein J, Prokopenko, Inga, Stančáková, Alena, Sung, Yun Ju, Tanaka, Toshiko, Teumer, Alexander, Van Vliet-Ostaptchouk, Jana V, Yengo, Loïc, Zhang, Weihua, Albrecht, Eva, Ärnlöv, Johan, Arscott, Gillian M, Bandinelli, Stefania, Barrett, Amy, Bellis, Claire, Bennett, Amanda J, Berne, Christian, Blüher, Matthias, Böhringer, Stefan, Bonnet, Fabrice, Böttcher, Yvonne, Bruinenberg, Marcel, Carba, Delia B, Caspersen, Ida H, Clarke, Robert, Daw, E Warwick, Deelen, Joris, Deelman, Ewa, Delgado, Graciela, Doney, Alex SF, Eklund, Niina, Erdos, Michael R, Estrada, Karol, Eury, Elodie, Friedrich, Nele, Garcia, Melissa E, Giedraitis, Vilmantas, Gigante, Bruna, Go, Alan S, Golay, Alain, Grallert, Harald, Grammer, Tanja B, Gräßler, Jürgen, Grewal, Jagvir, Groves, Christopher J, Haller, Toomas, Hallmans, Goran, Hartman, Catharina A, Hassinen, Maija, Hayward, Caroline, Heikkilä, Kauko, Herzig, Karl-Heinz, Helmer, Quinta, Hillege, Hans L, Holmen, Oddgeir, Hunt, Steven C, Isaacs, Aaron, Ittermann, Till, James, Alan L, Johansson, Ingegerd, Juliusdottir, Thorhildur, Kalafati, Ioanna-Panagiota, Kinnunen, Leena, Koenig, Wolfgang, Kooner, Ishminder K, Kratzer, Wolfgang, Lamina, Claudia, Leander, Karin, Lee, Nanette R, Lichtner, Peter, Lind, Lars, Lindström, Jaana, Lobbens, Stéphane, Lorentzon, Mattias, Mach, François, Magnusson, Patrik KE, Mahajan, Anubha, McArdle, Wendy L, Menni, Cristina, Merger, Sigrun, Mihailov, Evelin, Milani, Lili, Mills, Rebecca, Moayyeri, Alireza, Monda, Keri L, Mooijaart, Simon P, Mühleisen, Thomas W, Mulas, Antonella, Müller, Gabriele, Müller-Nurasyid, Martina, Nagaraja, Ramaiah, Nalls, Michael A, Narisu, Narisu, Glorioso, Nicola, Nolte, Ilja M, Olden, Matthias, Rayner, Nigel W, Renstrom, Frida, Ried, Janina S, Robertson, Neil R, Rose, Lynda M, Sanna, Serena, Scharnagl, Hubert, Scholtens, Salome, Sennblad, Bengt, Seufferlein, Thomas, Sitlani, Colleen M, Smith, Albert Vernon, Stirrups, Kathleen, Stringham, Heather M, Sundström, Johan, Swertz, Morris A, Swift, Amy J, Syvänen, Ann-Christine, Tayo, Bamidele O, Thorand, Barbara, Thorleifsson, Gudmar, Tomaschitz, Andreas, Troffa, Chiara, van Oort, Floor VA, Verweij, Niek, Vonk, Judith M, Waite, Lindsay L, Wennauer, Roman, Wilsgaard, Tom, Wojczynski, Mary K, Wong, Andrew, Zhang, Qunyuan, Zhao, Jing Hua, Brennan, Eoin P., Choi, Murim, Eriksson, Per, Folkersen, Lasse, Franco-Cereceda, Anders, Gharavi, Ali G, Hedman, Åsa K, Hivert, Marie-France, Huang, Jinyan, Kanoni, Stavroula, Karpe, Fredrik, Keildson, Sarah, Kiryluk, Krzysztof, Liang, Liming, Lifton, Richard P, Ma, Baoshan, McKnight, Amy J, McPherson, Ruth, Metspalu, Andres, Min, Josine L, Moffatt, Miriam F, Montgomery, Grant W, Murabito, Joanne M, Nicholson, George, Nyholt, Dale R, Olsson, Christian, Perry, John RB, Reinmaa, Eva, Salem, Rany M, Sandholm, Niina, Schadt, Eric E, Scott, Robert A, Stolk, Lisette, Vallejo, Edgar E., Westra, Harm-Jan, Zondervan, Krina T, Amouyel, Philippe, Arveiler, Dominique, Bakker, Stephan JL, Beilby, John, Bergman, Richard N, Blangero, John, Brown, Morris J, Burnier, Michel, Campbell, Harry, Chakravarti, Aravinda, Chines, Peter S, Claudi-Boehm, Simone, Collins, Francis S, Crawford, Dana C, Danesh, John, de Faire, Ulf, de Geus, Eco JC, Dörr, Marcus, Erbel, Raimund, Eriksson, Johan G, Farrall, Martin, Ferrannini, Ele, Ferrières, Jean, Forouhi, Nita G, Forrester, Terrence, Franco, Oscar H, Gansevoort, Ron T, Gieger, Christian, Gudnason, Vilmundur, Haiman, Christopher A, Harris, Tamara B, Hattersley, Andrew T, Heliövaara, Markku, Hicks, Andrew A, Hingorani, Aroon D, Hoffmann, Wolfgang, Hofman, Albert, Homuth, Georg, Humphries, Steve E, Hyppönen, Elina, Illig, Thomas, Jarvelin, Marjo-Riitta, Johansen, Berit, Jousilahti, Pekka, Jula, Antti M, Kaprio, Jaakko, Kee, Frank, Keinanen-Kiukaanniemi, Sirkka M, Kooner, Jaspal S, Kooperberg, Charles, Kovacs, Peter, Kraja, Aldi T, Kumari, Meena, Kuulasmaa, Kari, Kuusisto, Johanna, Lakka, Timo A, Langenberg, Claudia, Le Marchand, Loic, Lehtimäki, Terho, Lyssenko, Valeriya, Männistö, Satu, Marette, André, Matise, Tara C, McKenzie, Colin A, McKnight, Barbara, Musk, Arthur W, Möhlenkamp, Stefan, Morris, Andrew D, Nelis, Mari, Ohlsson, Claes, Oldehinkel, Albertine J, Ong, Ken K, Palmer, Lyle J, Penninx, Brenda W, Peters, Annette, Pramstaller, Peter P, Raitakari, Olli T, Rankinen, Tuomo, Rao, DC, Rice, Treva K, Ridker, Paul M, Ritchie, Marylyn D., Rudan, Igor, Salomaa, Veikko, Samani, Nilesh J, Saramies, Jouko, Sarzynski, Mark A, Schwarz, Peter EH, Shuldiner, Alan R, Staessen, Jan A, Steinthorsdottir, Valgerdur, Stolk, Ronald P, Strauch, Konstantin, Tönjes, Anke, Tremblay, Angelo, Tremoli, Elena, Vohl, Marie-Claude, Völker, Uwe, Vollenweider, Peter, Wilson, James F, Witteman, Jacqueline C, Adair, Linda S, Bochud, Murielle, Boehm, Bernhard O, Bornstein, Stefan R, Bouchard, Claude, Cauchi, Stéphane, Caulfield, Mark J, Chambers, John C, Chasman, Daniel I, Cooper, Richard S, Dedoussis, George, Ferrucci, Luigi, Froguel, Philippe, Grabe, Hans-Jörgen, Hamsten, Anders, Hui, Jennie, Hveem, Kristian, Jöckel, Karl-Heinz, Kivimaki, Mika, Kuh, Diana, Laakso, Markku, Liu, Yongmei, März, Winfried, Munroe, Patricia B, Njølstad, Inger, Oostra, Ben A, Palmer, Colin NA, Pedersen, Nancy L, Perola, Markus, Pérusse, Louis, Peters, Ulrike, Power, Chris, Quertermous, Thomas, Rauramaa, Rainer, Rivadeneira, Fernando, Saaristo, Timo E, Saleheen, Danish, Sinisalo, Juha, Slagboom, P Eline, Snieder, Harold, Spector, Tim D, Stefansson, Kari, Stumvoll, Michael, Tuomilehto, Jaakko, Uitterlinden, André G, Uusitupa, Matti, van der Harst, Pim, Veronesi, Giovanni, Walker, Mark, Wareham, Nicholas J, Watkins, Hugh, Wichmann, H-Erich, Abecasis, Goncalo R, Assimes, Themistocles L, Berndt, Sonja I, Boehnke, Michael, Borecki, Ingrid B, Deloukas, Panos, Franke, Lude, Frayling, Timothy M, Groop, Leif C, Hunter, David J., Kaplan, Robert C, O’Connell, Jeffrey R, Qi, Lu, Schlessinger, David, Strachan, David P, Thorsteinsdottir, Unnur, van Duijn, Cornelia M, Willer, Cristen J, Visscher, Peter M, Yang, Jian, Hirschhorn, Joel N, Zillikens, M Carola, McCarthy, Mark I, Speliotes, Elizabeth K, North, Kari E, Fox, Caroline S, Barroso, Inês, Franks, Paul W, Ingelsson, Erik, Heid, Iris M, Loos, Ruth JF, Cupples, L Adrienne, Morris, Andrew P, Lindgren, Cecilia M, and Mohlke, Karen L

Abstract

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, we conducted genome-wide association meta-analyses of waist and hip circumference-related traits in up to 224,459 individuals. We identified 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (WHRadjBMI) and an additional 19 loci newly associated with related waist and hip circumference measures (P<5×10−8). Twenty of the 49 WHRadjBMI loci showed significant sexual dimorphism, 19 of which displayed a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation, and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.

Published
2014
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194. Defining the role of common variation in the genomic and biological architecture of adult human height

Author

Wood, Andrew R, Esko, Tonu, Yang, Jian, Vedantam, Sailaja, Pers, Tune H, Gustafsson, Stefan, Chu, Audrey Y, Estrada, Karol, Luan, Jian’an, Kutalik, Zoltán, Amin, Najaf, Buchkovich, Martin L, Croteau-Chonka, Damien C, Day, Felix R, Duan, Yanan, Fall, Tove, Fehrmann, Rudolf, Ferreira, Teresa, Jackson, Anne U, Karjalainen, Juha, Lo, Ken Sin, Locke, Adam E, Mägi, Reedik, Mihailov, Evelin, Porcu, Eleonora, Randall, Joshua C, Scherag, André, Vinkhuyzen, Anna AE, Westra, Harm-Jan, Winkler, Thomas W, Workalemahu, Tsegaselassie, Zhao, Jing Hua, Absher, Devin, Albrecht, Eva, Anderson, Denise, Baron, Jeffrey, Beekman, Marian, Demirkan, Ayse, Ehret, Georg B, Feenstra, Bjarke, Feitosa, Mary F, Fischer, Krista, Fraser, Ross M, Goel, Anuj, Gong, Jian, Justice, Anne E, Kanoni, Stavroula, Kleber, Marcus E, Kristiansson, Kati, Lim, Unhee, Lotay, Vaneet, Lui, Julian C, Mangino, Massimo, Leach, Irene Mateo, Medina-Gomez, Carolina, Nalls, Michael A, Nyholt, Dale R, Palmer, Cameron D, Pasko, Dorota, Pechlivanis, Sonali, Prokopenko, Inga, Ried, Janina S, Ripke, Stephan, Shungin, Dmitry, Stancáková, Alena, Strawbridge, Rona J, Sung, Yun Ju, Tanaka, Toshiko, Teumer, Alexander, Trompet, Stella, van der Laan, Sander W, van Setten, Jessica, Van Vliet-Ostaptchouk, Jana V, Wang, Zhaoming, Yengo, Loïc, Zhang, Weihua, Afzal, Uzma, Ärnlöv, Johan, Arscott, Gillian M, Bandinelli, Stefania, Barrett, Amy, Bellis, Claire, Bennett, Amanda J, Berne, Christian, Blüher, Matthias, Bolton, Jennifer L, Böttcher, Yvonne, Boyd, Heather A, Bruinenberg, Marcel, Buckley, Brendan M, Buyske, Steven, Caspersen, Ida H, Chines, Peter S, Clarke, Robert, Claudi-Boehm, Simone, Cooper, Matthew, Daw, E Warwick, De Jong, Pim A, Deelen, Joris, Delgado, Graciela, Denny, Josh C, Dhonukshe-Rutten, Rosalie, Dimitriou, Maria, Doney, Alex SF, Dörr, Marcus, Eklund, Niina, Eury, Elodie, Folkersen, Lasse, Garcia, Melissa E, Geller, Frank, Giedraitis, Vilmantas, Go, Alan S, Grallert, Harald, Grammer, Tanja B, Gräßler, Jürgen, Grönberg, Henrik, de Groot, Lisette C.P.G.M., Groves, Christopher J, Haessler, Jeffrey, Hall, Per, Haller, Toomas, Hallmans, Goran, Hannemann, Anke, Hartman, Catharina A, Hassinen, Maija, Hayward, Caroline, Heard-Costa, Nancy L, Helmer, Quinta, Hemani, Gibran, Henders, Anjali K, Hillege, Hans L, Hlatky, Mark A, Hoffmann, Wolfgang, Hoffmann, Per, Holmen, Oddgeir, Houwing-Duistermaat, Jeanine J, Illig, Thomas, Isaacs, Aaron, James, Alan L, Jeff, Janina, Johansen, Berit, Johansson, Åsa, Jolley, Jennifer, Juliusdottir, Thorhildur, Junttila, Juhani, Kho, Abel N, Kinnunen, Leena, Klopp, Norman, Kocher, Thomas, Kratzer, Wolfgang, Lichtner, Peter, Lind, Lars, Lindström, Jaana, Lobbens, Stéphane, Lorentzon, Mattias, Lu, Yingchang, Lyssenko, Valeriya, Magnusson, Patrik KE, Mahajan, Anubha, Maillard, Marc, McArdle, Wendy L, McKenzie, Colin A, McLachlan, Stela, McLaren, Paul J, Menni, Cristina, Merger, Sigrun, Milani, Lili, Moayyeri, Alireza, Monda, Keri L, Morken, Mario A, Müller, Gabriele, Müller-Nurasyid, Martina, Musk, Arthur W, Narisu, Narisu, Nauck, Matthias, Nolte, Ilja M, Nöthen, Markus M, Oozageer, Laticia, Pilz, Stefan, Rayner, Nigel W, Renstrom, Frida, Robertson, Neil R, Rose, Lynda M, Roussel, Ronan, Sanna, Serena, Scharnagl, Hubert, Scholtens, Salome, Schumacher, Fredrick R, Schunkert, Heribert, Scott, Robert A, Sehmi, Joban, Seufferlein, Thomas, Shi, Jianxin, Silventoinen, Karri, Smit, Johannes H, Smith, Albert Vernon, Smolonska, Joanna, Stanton, Alice V, Stirrups, Kathleen, Stott, David J, Stringham, Heather M, Sundström, Johan, Swertz, Morris A, Syvänen, Ann-Christine, Tayo, Bamidele O, Thorleifsson, Gudmar, Tyrer, Jonathan P, van Dijk, Suzanne, van Schoor, Natasja M, van der Velde, Nathalie, van Heemst, Diana, van Oort, Floor VA, Vermeulen, Sita H, Verweij, Niek, Vonk, Judith M, Waite, Lindsay L, Waldenberger, Melanie, Wennauer, Roman, Wilkens, Lynne R, Willenborg, Christina, Wilsgaard, Tom, Wojczynski, Mary K, Wong, Andrew, Wright, Alan F, Zhang, Qunyuan, Arveiler, Dominique, Bakker, Stephan JL, Beilby, John, Bergman, Richard N, Bergmann, Sven, Biffar, Reiner, Blangero, John, Boomsma, Dorret I, Bornstein, Stefan R, Bovet, Pascal, Brambilla, Paolo, Brown, Morris J, Campbell, Harry, Caulfield, Mark J, Chakravarti, Aravinda, Collins, Rory, Collins, Francis S, Crawford, Dana C, Cupples, L Adrienne, Danesh, John, de Faire, Ulf, den Ruijter, Hester M, Erbel, Raimund, Erdmann, Jeanette, Eriksson, Johan G, Farrall, Martin, Ferrannini, Ele, Ferrières, Jean, Ford, Ian, Forouhi, Nita G, Forrester, Terrence, Gansevoort, Ron T, Gejman, Pablo V, Gieger, Christian, Golay, Alain, Gottesman, Omri, Gudnason, Vilmundur, Gyllensten, Ulf, Haas, David W, Hall, Alistair S, Harris, Tamara B, Hattersley, Andrew T, Heath, Andrew C, Hengstenberg, Christian, Hicks, Andrew A, Hindorff, Lucia A, Hingorani, Aroon D, Hofman, Albert, Hovingh, G Kees, Humphries, Steve E, Hunt, Steven C, Hypponen, Elina, Jacobs, Kevin B, Jarvelin, Marjo-Riitta, Jousilahti, Pekka, Jula, Antti M, Kaprio, Jaakko, Kastelein, John JP, Kayser, Manfred, Kee, Frank, Keinanen-Kiukaanniemi, Sirkka M, Kiemeney, Lambertus A, Kooner, Jaspal S, Kooperberg, Charles, Koskinen, Seppo, Kovacs, Peter, Kraja, Aldi T, Kumari, Meena, Kuusisto, Johanna, Lakka, Timo A, Langenberg, Claudia, Le Marchand, Loic, Lehtimäki, Terho, Lupoli, Sara, Madden, Pamela AF, Männistö, Satu, Manunta, Paolo, Marette, André, Matise, Tara C, McKnight, Barbara, Meitinger, Thomas, Moll, Frans L, Montgomery, Grant W, Morris, Andrew D, Morris, Andrew P, Murray, Jeffrey C, Nelis, Mari, Ohlsson, Claes, Oldehinkel, Albertine J, Ong, Ken K, Ouwehand, Willem H, Pasterkamp, Gerard, Peters, Annette, Pramstaller, Peter P, Price, Jackie F, Qi, Lu, Raitakari, Olli T, Rankinen, Tuomo, Rao, DC, Rice, Treva K, Ritchie, Marylyn, Rudan, Igor, Salomaa, Veikko, Samani, Nilesh J, Saramies, Jouko, Sarzynski, Mark A, Schwarz, Peter EH, Sebert, Sylvain, Sever, Peter, Shuldiner, Alan R, Sinisalo, Juha, Steinthorsdottir, Valgerdur, Stolk, Ronald P, Tardif, Jean-Claude, Tönjes, Anke, Tremblay, Angelo, Tremoli, Elena, Virtamo, Jarmo, Vohl, Marie-Claude, Amouyel, Philippe, Asselbergs, Folkert W, Assimes, Themistocles L, Bochud, Murielle, Boehm, Bernhard O, Boerwinkle, Eric, Bottinger, Erwin P, Bouchard, Claude, Cauchi, Stéphane, Chambers, John C, Chanock, Stephen J, Cooper, Richard S, de Bakker, Paul IW, Dedoussis, George, Ferrucci, Luigi, Franks, Paul W, Froguel, Philippe, Groop, Leif C, Haiman, Christopher A, Hamsten, Anders, Hayes, M Geoffrey, Hui, Jennie, Hunter, David J., Hveem, Kristian, Jukema, J Wouter, Kaplan, Robert C, Kivimaki, Mika, Kuh, Diana, Laakso, Markku, Liu, Yongmei, Martin, Nicholas G, März, Winfried, Melbye, Mads, Moebus, Susanne, Munroe, Patricia B, Njølstad, Inger, Oostra, Ben A, Palmer, Colin NA, Pedersen, Nancy L, Perola, Markus, Pérusse, Louis, Peters, Ulrike, Powell, Joseph E, Power, Chris, Quertermous, Thomas, Rauramaa, Rainer, Reinmaa, Eva, Ridker, Paul M, Rivadeneira, Fernando, Rotter, Jerome I, Saaristo, Timo E, Saleheen, Danish, Schlessinger, David, Slagboom, P Eline, Snieder, Harold, Spector, Tim D, Strauch, Konstantin, Stumvoll, Michael, Tuomilehto, Jaakko, Uusitupa, Matti, van der Harst, Pim, Völzke, Henry, Walker, Mark, Wareham, Nicholas J, Watkins, Hugh, Wichmann, H-Erich, Wilson, James F, Zanen, Pieter, Deloukas, Panos, Heid, Iris M, Lindgren, Cecilia M, Mohlke, Karen L, Speliotes, Elizabeth K, Thorsteinsdottir, Unnur, Barroso, Inês, Fox, Caroline S, North, Kari E, Strachan, David P, Beckmann, Jacques S., Berndt, Sonja I, Boehnke, Michael, Borecki, Ingrid B, McCarthy, Mark I, Metspalu, Andres, Stefansson, Kari, Uitterlinden, André G, van Duijn, Cornelia M, Franke, Lude, Willer, Cristen J, Price, Alkes L., Lettre, Guillaume, Loos, Ruth JF, Weedon, Michael N, Ingelsson, Erik, O’Connell, Jeffrey R, Abecasis, Goncalo R, Chasman, Daniel I, Goddard, Michael E, Visscher, Peter M, Hirschhorn, Joel N, and Frayling, Timothy M

Abstract

Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explain one-fifth of heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ~2,000, ~3,700 and ~9,500 SNPs explained ~21%, ~24% and ~29% of phenotypic variance. Furthermore, all common variants together captured the majority (60%) of heritability. The 697 variants clustered in 423 loci enriched for genes, pathways, and tissue-types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/beta-catenin, and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.

Published
2014
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