%0 Journal Article %J Nature %D 2015 %T Genetic studies of body mass index yield new insights for obesity biology. %A Locke, Adam E %A Kahali, Bratati %A Berndt, Sonja I %A Justice, Anne E %A Pers, Tune H %A Day, Felix R %A Powell, Corey %A Vedantam, Sailaja %A Buchkovich, Martin L %A Yang, Jian %A Croteau-Chonka, Damien C %A Esko, Tõnu %A Fall, Tove %A Ferreira, Teresa %A Gustafsson, Stefan %A Kutalik, Zoltán %A Luan, Jian'an %A Mägi, Reedik %A Randall, Joshua C %A Winkler, Thomas W %A Wood, Andrew R %A Workalemahu, Tsegaselassie %A Faul, Jessica D %A Smith, Jennifer A %A Hua Zhao, Jing %A Zhao, Wei %A Chen, Jin %A Fehrmann, Rudolf %A Hedman, Åsa K %A Karjalainen, Juha %A Schmidt, Ellen M %A Absher, Devin %A Amin, Najaf %A Anderson, Denise %A Beekman, Marian %A Bolton, Jennifer L %A Bragg-Gresham, Jennifer L %A Buyske, Steven %A Demirkan, Ayse %A Deng, Guohong %A Ehret, Georg B %A Feenstra, Bjarke %A Feitosa, Mary F %A Fischer, Krista %A Goel, Anuj %A Gong, Jian %A Jackson, Anne U %A Kanoni, Stavroula %A Kleber, Marcus E %A Kristiansson, Kati %A Lim, Unhee %A Lotay, Vaneet %A Mangino, Massimo %A Mateo Leach, Irene %A Medina-Gomez, Carolina %A Medland, Sarah E %A Nalls, Michael A %A Palmer, Cameron D %A Pasko, Dorota %A Pechlivanis, Sonali %A Peters, Marjolein J %A Prokopenko, Inga %A Shungin, Dmitry %A Stančáková, Alena %A Strawbridge, Rona J %A Ju Sung, Yun %A Tanaka, Toshiko %A Teumer, Alexander %A Trompet, Stella %A van der Laan, Sander W %A van Setten, Jessica %A Van Vliet-Ostaptchouk, Jana V %A Wang, Zhaoming %A Yengo, Loic %A Zhang, Weihua %A Isaacs, Aaron %A Albrecht, Eva %A Arnlöv, Johan %A Arscott, Gillian M %A Attwood, Antony P %A Bandinelli, Stefania %A Barrett, Amy %A Bas, Isabelita N %A Bellis, Claire %A Bennett, Amanda J %A Berne, Christian %A Blagieva, Roza %A Blüher, Matthias %A Böhringer, Stefan %A Bonnycastle, Lori L %A Böttcher, Yvonne %A Boyd, Heather A %A Bruinenberg, Marcel %A Caspersen, Ida H %A Ida Chen, Yii-Der %A Clarke, Robert %A Daw, E Warwick %A de Craen, Anton J M %A Delgado, Graciela %A Dimitriou, Maria %A Doney, Alex S F %A Eklund, Niina %A Estrada, Karol %A Eury, Elodie %A Folkersen, Lasse %A Fraser, Ross M %A Garcia, Melissa E %A Geller, Frank %A Giedraitis, Vilmantas %A Gigante, Bruna %A Go, Alan S %A Golay, Alain %A Goodall, Alison H %A Gordon, Scott D %A Gorski, Mathias %A Grabe, Hans-Jörgen %A Grallert, Harald %A Grammer, Tanja B %A Gräßler, Jürgen %A Grönberg, Henrik %A Groves, Christopher J %A Gusto, Gaëlle %A Haessler, Jeffrey %A Hall, Per %A Haller, Toomas %A Hallmans, Goran %A Hartman, Catharina A %A Hassinen, Maija %A Hayward, Caroline %A Heard-Costa, Nancy L %A Helmer, Quinta %A Hengstenberg, Christian %A Holmen, Oddgeir %A Hottenga, Jouke-Jan %A James, Alan L %A Jeff, Janina M %A Johansson, Åsa %A Jolley, Jennifer %A Juliusdottir, Thorhildur %A Kinnunen, Leena %A Koenig, Wolfgang %A Koskenvuo, Markku %A Kratzer, Wolfgang %A Laitinen, Jaana %A Lamina, Claudia %A Leander, Karin %A Lee, Nanette R %A Lichtner, Peter %A Lind, Lars %A Lindström, Jaana %A Sin Lo, Ken %A Lobbens, Stéphane %A Lorbeer, Roberto %A Lu, Yingchang %A Mach, François %A Magnusson, Patrik K E %A Mahajan, Anubha %A McArdle, Wendy L %A McLachlan, Stela %A Menni, Cristina %A Merger, Sigrun %A Mihailov, Evelin %A Milani, Lili %A Moayyeri, Alireza %A Monda, Keri L %A Morken, Mario A %A Mulas, Antonella %A Müller, Gabriele %A Müller-Nurasyid, Martina %A Musk, Arthur W %A Nagaraja, Ramaiah %A Nöthen, Markus M %A Nolte, Ilja M %A Pilz, Stefan %A Rayner, Nigel W %A Renstrom, Frida %A Rettig, Rainer %A Ried, Janina S %A Ripke, Stephan %A Robertson, Neil R %A Rose, Lynda M %A Sanna, Serena %A Scharnagl, Hubert %A Scholtens, Salome %A Schumacher, Fredrick R %A Scott, William R %A Seufferlein, Thomas %A Shi, Jianxin %A Vernon Smith, Albert %A Smolonska, Joanna %A Stanton, Alice V %A Steinthorsdottir, Valgerdur %A Stirrups, Kathleen %A Stringham, Heather M %A Sundström, Johan %A Swertz, Morris A %A Swift, Amy J %A Syvänen, Ann-Christine %A Tan, Sian-Tsung %A Tayo, Bamidele O %A Thorand, Barbara %A Thorleifsson, Gudmar %A Tyrer, Jonathan P %A Uh, Hae-Won %A Vandenput, Liesbeth %A Verhulst, Frank C %A Vermeulen, Sita H %A Verweij, Niek %A Vonk, Judith M %A Waite, Lindsay L %A Warren, Helen R %A Waterworth, Dawn %A Weedon, Michael N %A Wilkens, Lynne R %A Willenborg, Christina %A Wilsgaard, Tom %A Wojczynski, Mary K %A Wong, Andrew %A Wright, Alan F %A Zhang, Qunyuan %A Brennan, Eoin P %A Choi, Murim %A Dastani, Zari %A Drong, Alexander W %A Eriksson, Per %A Franco-Cereceda, Anders %A Gådin, Jesper R %A Gharavi, Ali G %A Goddard, Michael E %A Handsaker, Robert E %A Huang, Jinyan %A Karpe, Fredrik %A Kathiresan, Sekar %A Keildson, Sarah %A Kiryluk, Krzysztof %A Kubo, Michiaki %A Lee, Jong-Young %A Liang, Liming %A Lifton, Richard P %A Ma, Baoshan %A McCarroll, Steven A %A McKnight, Amy J %A Min, Josine L %A Moffatt, Miriam F %A Montgomery, Grant W %A Murabito, Joanne M %A Nicholson, George %A Nyholt, Dale R %A Okada, Yukinori %A Perry, John R B %A Dorajoo, Rajkumar %A Reinmaa, Eva %A Salem, Rany M %A Sandholm, Niina %A Scott, Robert A %A Stolk, Lisette %A Takahashi, Atsushi %A Tanaka, Toshihiro %A Van't Hooft, Ferdinand M %A Vinkhuyzen, Anna A E %A Westra, Harm-Jan %A Zheng, Wei %A Zondervan, Krina T %A Heath, Andrew C %A Arveiler, Dominique %A Bakker, Stephan J L %A Beilby, John %A Bergman, Richard N %A Blangero, John %A Bovet, Pascal %A Campbell, Harry %A Caulfield, Mark J %A Cesana, Giancarlo %A Chakravarti, Aravinda %A Chasman, Daniel I %A Chines, Peter S %A Collins, Francis S %A Crawford, Dana C %A Cupples, L Adrienne %A Cusi, Daniele %A Danesh, John %A de Faire, Ulf %A den Ruijter, Hester M %A Dominiczak, Anna F %A Erbel, Raimund %A Erdmann, Jeanette %A Eriksson, Johan G %A Farrall, Martin %A Felix, Stephan B %A Ferrannini, Ele %A Ferrières, Jean %A Ford, Ian %A Forouhi, Nita G %A Forrester, Terrence %A Franco, Oscar H %A Gansevoort, Ron T %A Gejman, Pablo V %A Gieger, Christian %A Gottesman, Omri %A Gudnason, Vilmundur %A Gyllensten, Ulf %A Hall, Alistair S %A Harris, Tamara B %A Hattersley, Andrew T %A Hicks, Andrew A %A Hindorff, Lucia A %A Hingorani, Aroon D %A Hofman, Albert %A Homuth, Georg %A Hovingh, G Kees %A Humphries, Steve E %A Hunt, Steven C %A Hyppönen, Elina %A Illig, Thomas %A Jacobs, Kevin B %A Järvelin, Marjo-Riitta %A Jöckel, Karl-Heinz %A Johansen, Berit %A Jousilahti, Pekka %A Jukema, J Wouter %A Jula, Antti M %A Kaprio, Jaakko %A Kastelein, John J P %A Keinanen-Kiukaanniemi, Sirkka M %A Kiemeney, Lambertus A %A Knekt, Paul %A Kooner, Jaspal S %A Kooperberg, Charles %A Kovacs, Peter %A Kraja, Aldi T %A Kumari, Meena %A Kuusisto, Johanna %A Lakka, Timo A %A Langenberg, Claudia %A Le Marchand, Loic %A Lehtimäki, Terho %A Lyssenko, Valeriya %A Männistö, Satu %A Marette, André %A Matise, Tara C %A McKenzie, Colin A %A McKnight, Barbara %A Moll, Frans L %A Morris, Andrew D %A Morris, Andrew P %A Murray, Jeffrey C %A Nelis, Mari %A Ohlsson, Claes %A Oldehinkel, Albertine J %A Ong, Ken K %A Madden, Pamela A F %A Pasterkamp, Gerard %A Peden, John F %A Peters, Annette %A Postma, Dirkje S %A Pramstaller, Peter P %A Price, Jackie F %A Qi, Lu %A Raitakari, Olli T %A Rankinen, Tuomo %A Rao, D C %A Rice, Treva K %A Ridker, Paul M %A Rioux, John D %A Ritchie, Marylyn D %A Rudan, Igor %A Salomaa, Veikko %A Samani, Nilesh J %A Saramies, Jouko %A Sarzynski, Mark A %A Schunkert, Heribert %A Schwarz, Peter E H %A Sever, Peter %A Shuldiner, Alan R %A Sinisalo, Juha %A Stolk, Ronald P %A Strauch, Konstantin %A Tönjes, Anke %A Trégouët, David-Alexandre %A Tremblay, Angelo %A Tremoli, Elena %A Virtamo, Jarmo %A Vohl, Marie-Claude %A Völker, Uwe %A Waeber, Gerard %A Willemsen, Gonneke %A Witteman, Jacqueline C %A Zillikens, M Carola %A Adair, Linda S %A Amouyel, Philippe %A Asselbergs, Folkert W %A Assimes, Themistocles L %A Bochud, Murielle %A Boehm, Bernhard O %A Boerwinkle, Eric %A Bornstein, Stefan R %A Bottinger, Erwin P %A Bouchard, Claude %A Cauchi, Stéphane %A Chambers, John C %A Chanock, Stephen J %A Cooper, Richard S %A de Bakker, Paul I W %A Dedoussis, George %A Ferrucci, Luigi %A Franks, Paul W %A Froguel, Philippe %A Groop, Leif C %A Haiman, Christopher A %A Hamsten, Anders %A Hui, Jennie %A Hunter, David J %A Hveem, Kristian %A Kaplan, Robert C %A Kivimaki, Mika %A Kuh, Diana %A Laakso, Markku %A Liu, Yongmei %A Martin, Nicholas G %A März, Winfried %A Melbye, Mads %A Metspalu, Andres %A Moebus, Susanne %A Munroe, Patricia B %A Njølstad, Inger %A Oostra, Ben A %A Palmer, Colin N A %A Pedersen, Nancy L %A Perola, Markus %A Pérusse, Louis %A Peters, Ulrike %A Power, Chris %A Quertermous, Thomas %A Rauramaa, Rainer %A Rivadeneira, Fernando %A Saaristo, Timo E %A Saleheen, Danish %A Sattar, Naveed %A Schadt, Eric E %A Schlessinger, David %A Slagboom, P Eline %A Snieder, Harold %A Spector, Tim D %A Thorsteinsdottir, Unnur %A Stumvoll, Michael %A Tuomilehto, Jaakko %A Uitterlinden, André G %A Uusitupa, Matti %A van der Harst, Pim %A Walker, Mark %A Wallaschofski, Henri %A Wareham, Nicholas J %A Watkins, Hugh %A Weir, David R %A Wichmann, H-Erich %A Wilson, James F %A Zanen, Pieter %A Borecki, Ingrid B %A Deloukas, Panos %A Fox, Caroline S %A Heid, Iris M %A O'Connell, Jeffrey R %A Strachan, David P %A Stefansson, Kari %A van Duijn, Cornelia M %A Abecasis, Goncalo R %A Franke, Lude %A Frayling, Timothy M %A McCarthy, Mark I %A Visscher, Peter M %A Scherag, André %A Willer, Cristen J %A Boehnke, Michael %A Mohlke, Karen L %A Lindgren, Cecilia M %A Beckmann, Jacques S %A Barroso, Inês %A North, Kari E %A Ingelsson, Erik %A Hirschhorn, Joel N %A Loos, Ruth J F %A Speliotes, Elizabeth K %K Adipogenesis %K Adiposity %K Age Factors %K Body Mass Index %K Continental Population Groups %K Energy Metabolism %K Europe %K Female %K Genetic Predisposition to Disease %K Genome-Wide Association Study %K Glutamic Acid %K Humans %K Insulin %K Male %K Obesity %K Polymorphism, Single Nucleotide %K Quantitative Trait Loci %K Synapses %X

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 up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 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 ∼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 system in 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.

%B Nature %V 518 %P 197-206 %8 2015 Feb 12 %G eng %N 7538 %1 http://www.ncbi.nlm.nih.gov/pubmed/25673413?dopt=Abstract %R 10.1038/nature14177 %0 Journal Article %J Nature %D 2015 %T New genetic loci link adipose and insulin biology to body fat distribution. %A Shungin, Dmitry %A Winkler, Thomas W %A Croteau-Chonka, Damien C %A Ferreira, Teresa %A Locke, Adam E %A Mägi, Reedik %A Strawbridge, Rona J %A Pers, Tune H %A Fischer, Krista %A Justice, Anne E %A Workalemahu, Tsegaselassie %A Wu, Joseph M W %A Buchkovich, Martin L %A Heard-Costa, Nancy L %A Roman, Tamara S %A Drong, Alexander W %A Song, Ci %A Gustafsson, Stefan %A Day, Felix R %A Esko, Tõnu %A Fall, Tove %A Kutalik, Zoltán %A Luan, Jian'an %A Randall, Joshua C %A Scherag, André %A Vedantam, Sailaja %A Wood, Andrew R %A Chen, Jin %A Fehrmann, Rudolf %A Karjalainen, Juha %A Kahali, Bratati %A Liu, Ching-Ti %A Schmidt, Ellen M %A Absher, Devin %A Amin, Najaf %A Anderson, Denise %A Beekman, Marian %A Bragg-Gresham, Jennifer L %A Buyske, Steven %A Demirkan, Ayse %A Ehret, Georg B %A Feitosa, Mary F %A Goel, Anuj %A Jackson, Anne U %A Johnson, Toby %A Kleber, Marcus E %A Kristiansson, Kati %A Mangino, Massimo %A Mateo Leach, Irene %A Medina-Gomez, Carolina %A Palmer, Cameron D %A Pasko, Dorota %A Pechlivanis, Sonali %A Peters, Marjolein J %A Prokopenko, Inga %A Stančáková, Alena %A Ju Sung, Yun %A Tanaka, Toshiko %A Teumer, Alexander %A Van Vliet-Ostaptchouk, Jana V %A Yengo, Loic %A Zhang, Weihua %A Albrecht, Eva %A Arnlöv, Johan %A Arscott, Gillian M %A Bandinelli, Stefania %A Barrett, Amy %A Bellis, Claire %A Bennett, Amanda J %A Berne, Christian %A Blüher, Matthias %A Böhringer, Stefan %A Bonnet, Fabrice %A Böttcher, Yvonne %A Bruinenberg, Marcel %A Carba, Delia B %A Caspersen, Ida H %A Clarke, Robert %A Daw, E Warwick %A Deelen, Joris %A Deelman, Ewa %A Delgado, Graciela %A Doney, Alex S F %A Eklund, Niina %A Erdos, Michael R %A Estrada, Karol %A Eury, Elodie %A Friedrich, Nele %A Garcia, Melissa E %A Giedraitis, Vilmantas %A Gigante, Bruna %A Go, Alan S %A Golay, Alain %A Grallert, Harald %A Grammer, Tanja B %A Gräßler, Jürgen %A Grewal, Jagvir %A Groves, Christopher J %A Haller, Toomas %A Hallmans, Goran %A Hartman, Catharina A %A Hassinen, Maija %A Hayward, Caroline %A Heikkilä, Kauko %A Herzig, Karl-Heinz %A Helmer, Quinta %A Hillege, Hans L %A Holmen, Oddgeir %A Hunt, Steven C %A Isaacs, Aaron %A Ittermann, Till %A James, Alan L %A Johansson, Ingegerd %A Juliusdottir, Thorhildur %A Kalafati, Ioanna-Panagiota %A Kinnunen, Leena %A Koenig, Wolfgang %A Kooner, Ishminder K %A Kratzer, Wolfgang %A Lamina, Claudia %A Leander, Karin %A Lee, Nanette R %A Lichtner, Peter %A Lind, Lars %A Lindström, Jaana %A Lobbens, Stéphane %A Lorentzon, Mattias %A Mach, François %A Magnusson, Patrik K E %A Mahajan, Anubha %A McArdle, Wendy L %A Menni, Cristina %A Merger, Sigrun %A Mihailov, Evelin %A Milani, Lili %A Mills, Rebecca %A Moayyeri, Alireza %A Monda, Keri L %A Mooijaart, Simon P %A Mühleisen, Thomas W %A Mulas, Antonella %A Müller, Gabriele %A Müller-Nurasyid, Martina %A Nagaraja, Ramaiah %A Nalls, Michael A %A Narisu, Narisu %A Glorioso, Nicola %A Nolte, Ilja M %A Olden, Matthias %A Rayner, Nigel W %A Renstrom, Frida %A Ried, Janina S %A Robertson, Neil R %A Rose, Lynda M %A Sanna, Serena %A Scharnagl, Hubert %A Scholtens, Salome %A Sennblad, Bengt %A Seufferlein, Thomas %A Sitlani, Colleen M %A Vernon Smith, Albert %A Stirrups, Kathleen %A Stringham, Heather M %A Sundström, Johan %A Swertz, Morris A %A Swift, Amy J %A Syvänen, Ann-Christine %A Tayo, Bamidele O %A Thorand, Barbara %A Thorleifsson, Gudmar %A Tomaschitz, Andreas %A Troffa, Chiara %A van Oort, Floor V A %A Verweij, Niek %A Vonk, Judith M %A Waite, Lindsay L %A Wennauer, Roman %A Wilsgaard, Tom %A Wojczynski, Mary K %A Wong, Andrew %A Zhang, Qunyuan %A Hua Zhao, Jing %A Brennan, Eoin P %A Choi, Murim %A Eriksson, Per %A Folkersen, Lasse %A Franco-Cereceda, Anders %A Gharavi, Ali G %A Hedman, Åsa K %A Hivert, Marie-France %A Huang, Jinyan %A Kanoni, Stavroula %A Karpe, Fredrik %A Keildson, Sarah %A Kiryluk, Krzysztof %A Liang, Liming %A Lifton, Richard P %A Ma, Baoshan %A McKnight, Amy J %A McPherson, Ruth %A Metspalu, Andres %A Min, Josine L %A Moffatt, Miriam F %A Montgomery, Grant W %A Murabito, Joanne M %A Nicholson, George %A Nyholt, Dale R %A Olsson, Christian %A Perry, John R B %A Reinmaa, Eva %A Salem, Rany M %A Sandholm, Niina %A Schadt, Eric E %A Scott, Robert A %A Stolk, Lisette %A Vallejo, Edgar E %A Westra, Harm-Jan %A Zondervan, Krina T %A Amouyel, Philippe %A Arveiler, Dominique %A Bakker, Stephan J L %A Beilby, John %A Bergman, Richard N %A Blangero, John %A Brown, Morris J %A Burnier, Michel %A Campbell, Harry %A Chakravarti, Aravinda %A Chines, Peter S %A Claudi-Boehm, Simone %A Collins, Francis S %A Crawford, Dana C %A Danesh, John %A de Faire, Ulf %A de Geus, Eco J C %A Dörr, Marcus %A Erbel, Raimund %A Eriksson, Johan G %A Farrall, Martin %A Ferrannini, Ele %A Ferrières, Jean %A Forouhi, Nita G %A Forrester, Terrence %A Franco, Oscar H %A Gansevoort, Ron T %A Gieger, Christian %A Gudnason, Vilmundur %A Haiman, Christopher A %A Harris, Tamara B %A Hattersley, Andrew T %A Heliövaara, Markku %A Hicks, Andrew A %A Hingorani, Aroon D %A Hoffmann, Wolfgang %A Hofman, Albert %A Homuth, Georg %A Humphries, Steve E %A Hyppönen, Elina %A Illig, Thomas %A Järvelin, Marjo-Riitta %A Johansen, Berit %A Jousilahti, Pekka %A Jula, Antti M %A Kaprio, Jaakko %A Kee, Frank %A Keinanen-Kiukaanniemi, Sirkka M %A Kooner, Jaspal S %A Kooperberg, Charles %A Kovacs, Peter %A Kraja, Aldi T %A Kumari, Meena %A Kuulasmaa, Kari %A Kuusisto, Johanna %A Lakka, Timo A %A Langenberg, Claudia %A Le Marchand, Loic %A Lehtimäki, Terho %A Lyssenko, Valeriya %A Männistö, Satu %A Marette, André %A Matise, Tara C %A McKenzie, Colin A %A McKnight, Barbara %A Musk, Arthur W %A Möhlenkamp, Stefan %A Morris, Andrew D %A Nelis, Mari %A Ohlsson, Claes %A Oldehinkel, Albertine J %A Ong, Ken K %A Palmer, Lyle J %A Penninx, Brenda W %A Peters, Annette %A Pramstaller, Peter P %A Raitakari, Olli T %A Rankinen, Tuomo %A Rao, D C %A Rice, Treva K %A Ridker, Paul M %A Ritchie, Marylyn D %A Rudan, Igor %A Salomaa, Veikko %A Samani, Nilesh J %A Saramies, Jouko %A Sarzynski, Mark A %A Schwarz, Peter E H %A Shuldiner, Alan R %A Staessen, Jan A %A Steinthorsdottir, Valgerdur %A Stolk, Ronald P %A Strauch, Konstantin %A Tönjes, Anke %A Tremblay, Angelo %A Tremoli, Elena %A Vohl, Marie-Claude %A Völker, Uwe %A Vollenweider, Peter %A Wilson, James F %A Witteman, Jacqueline C %A Adair, Linda S %A Bochud, Murielle %A Boehm, Bernhard O %A Bornstein, Stefan R %A Bouchard, Claude %A Cauchi, Stéphane %A Caulfield, Mark J %A Chambers, John C %A Chasman, Daniel I %A Cooper, Richard S %A Dedoussis, George %A Ferrucci, Luigi %A Froguel, Philippe %A Grabe, Hans-Jörgen %A Hamsten, Anders %A Hui, Jennie %A Hveem, Kristian %A Jöckel, Karl-Heinz %A Kivimaki, Mika %A Kuh, Diana %A Laakso, Markku %A Liu, Yongmei %A März, Winfried %A Munroe, Patricia B %A Njølstad, Inger %A Oostra, Ben A %A Palmer, Colin N A %A Pedersen, Nancy L %A Perola, Markus %A Pérusse, Louis %A Peters, Ulrike %A Power, Chris %A Quertermous, Thomas %A Rauramaa, Rainer %A Rivadeneira, Fernando %A Saaristo, Timo E %A Saleheen, Danish %A Sinisalo, Juha %A Slagboom, P Eline %A Snieder, Harold %A Spector, Tim D %A Thorsteinsdottir, Unnur %A Stumvoll, Michael %A Tuomilehto, Jaakko %A Uitterlinden, André G %A Uusitupa, Matti %A van der Harst, Pim %A Veronesi, Giovanni %A Walker, Mark %A Wareham, Nicholas J %A Watkins, Hugh %A Wichmann, H-Erich %A Abecasis, Goncalo R %A Assimes, Themistocles L %A Berndt, Sonja I %A Boehnke, Michael %A Borecki, Ingrid B %A Deloukas, Panos %A Franke, Lude %A Frayling, Timothy M %A Groop, Leif C %A Hunter, David J %A Kaplan, Robert C %A O'Connell, Jeffrey R %A Qi, Lu %A Schlessinger, David %A Strachan, David P %A Stefansson, Kari %A van Duijn, Cornelia M %A Willer, Cristen J %A Visscher, Peter M %A Yang, Jian %A Hirschhorn, Joel N %A Zillikens, M Carola %A McCarthy, Mark I %A Speliotes, Elizabeth K %A North, Kari E %A Fox, Caroline S %A Barroso, Inês %A Franks, Paul W %A Ingelsson, Erik %A Heid, Iris M %A Loos, Ruth J F %A Cupples, L Adrienne %A Morris, Andrew P %A Lindgren, Cecilia M %A Mohlke, Karen L %K Adipocytes %K Adipogenesis %K Adipose Tissue %K Age Factors %K Body Fat Distribution %K Body Mass Index %K Continental Population Groups %K Epigenesis, Genetic %K Europe %K Female %K Genome, Human %K Genome-Wide Association Study %K Humans %K Insulin %K Insulin Resistance %K Male %K Models, Biological %K Neovascularization, Physiologic %K Obesity %K Polymorphism, Single Nucleotide %K Quantitative Trait Loci %K Sex Characteristics %K Transcription, Genetic %K Waist-Hip Ratio %X

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 × 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.

%B Nature %V 518 %P 187-96 %8 2015 Feb 12 %G eng %N 7538 %1 http://www.ncbi.nlm.nih.gov/pubmed/25673412?dopt=Abstract %R 10.1038/nature14132 %0 Journal Article %J Nat Genet %D 2014 %T Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization. %A Arking, Dan E %A Pulit, Sara L %A Crotti, Lia %A van der Harst, Pim %A Munroe, Patricia B %A Koopmann, Tamara T %A Sotoodehnia, Nona %A Rossin, Elizabeth J %A Morley, Michael %A Wang, Xinchen %A Johnson, Andrew D %A Lundby, Alicia %A Gudbjartsson, Daniel F %A Noseworthy, Peter A %A Eijgelsheim, Mark %A Bradford, Yuki %A Tarasov, Kirill V %A Dörr, Marcus %A Müller-Nurasyid, Martina %A Lahtinen, Annukka M %A Nolte, Ilja M %A Smith, Albert Vernon %A Bis, Joshua C %A Isaacs, Aaron %A Newhouse, Stephen J %A Evans, Daniel S %A Post, Wendy S %A Waggott, Daryl %A Lyytikäinen, Leo-Pekka %A Hicks, Andrew A %A Eisele, Lewin %A Ellinghaus, David %A Hayward, Caroline %A Navarro, Pau %A Ulivi, Sheila %A Tanaka, Toshiko %A Tester, David J %A Chatel, Stéphanie %A Gustafsson, Stefan %A Kumari, Meena %A Morris, Richard W %A Naluai, Åsa T %A Padmanabhan, Sandosh %A Kluttig, Alexander %A Strohmer, Bernhard %A Panayiotou, Andrie G %A Torres, Maria %A Knoflach, Michael %A Hubacek, Jaroslav A %A Slowikowski, Kamil %A Raychaudhuri, Soumya %A Kumar, Runjun D %A Harris, Tamara B %A Launer, Lenore J %A Shuldiner, Alan R %A Alonso, Alvaro %A Bader, Joel S %A Ehret, Georg %A Huang, Hailiang %A Kao, W H Linda %A Strait, James B %A Macfarlane, Peter W %A Brown, Morris %A Caulfield, Mark J %A Samani, Nilesh J %A Kronenberg, Florian %A Willeit, Johann %A Smith, J Gustav %A Greiser, Karin H %A Meyer Zu Schwabedissen, Henriette %A Werdan, Karl %A Carella, Massimo %A Zelante, Leopoldo %A Heckbert, Susan R %A Psaty, Bruce M %A Rotter, Jerome I %A Kolcic, Ivana %A Polasek, Ozren %A Wright, Alan F %A Griffin, Maura %A Daly, Mark J %A Arnar, David O %A Holm, Hilma %A Thorsteinsdottir, Unnur %A Denny, Joshua C %A Roden, Dan M %A Zuvich, Rebecca L %A Emilsson, Valur %A Plump, Andrew S %A Larson, Martin G %A O'Donnell, Christopher J %A Yin, Xiaoyan %A Bobbo, Marco %A d'Adamo, Adamo P %A Iorio, Annamaria %A Sinagra, Gianfranco %A Carracedo, Angel %A Cummings, Steven R %A Nalls, Michael A %A Jula, Antti %A Kontula, Kimmo K %A Marjamaa, Annukka %A Oikarinen, Lasse %A Perola, Markus %A Porthan, Kimmo %A Erbel, Raimund %A Hoffmann, Per %A Jöckel, Karl-Heinz %A Kälsch, Hagen %A Nöthen, Markus M %A den Hoed, Marcel %A Loos, Ruth J F %A Thelle, Dag S %A Gieger, Christian %A Meitinger, Thomas %A Perz, Siegfried %A Peters, Annette %A Prucha, Hanna %A Sinner, Moritz F %A Waldenberger, Melanie %A de Boer, Rudolf A %A Franke, Lude %A van der Vleuten, Pieter A %A Beckmann, Britt Maria %A Martens, Eimo %A Bardai, Abdennasser %A Hofman, Nynke %A Wilde, Arthur A M %A Behr, Elijah R %A Dalageorgou, Chrysoula %A Giudicessi, John R %A Medeiros-Domingo, Argelia %A Barc, Julien %A Kyndt, Florence %A Probst, Vincent %A Ghidoni, Alice %A Insolia, Roberto %A Hamilton, Robert M %A Scherer, Stephen W %A Brandimarto, Jeffrey %A Margulies, Kenneth %A Moravec, Christine E %A del Greco M, Fabiola %A Fuchsberger, Christian %A O'Connell, Jeffrey R %A Lee, Wai K %A Watt, Graham C M %A Campbell, Harry %A Wild, Sarah H %A El Mokhtari, Nour E %A Frey, Norbert %A Asselbergs, Folkert W %A Mateo Leach, Irene %A Navis, Gerjan %A van den Berg, Maarten P %A van Veldhuisen, Dirk J %A Kellis, Manolis %A Krijthe, Bouwe P %A Franco, Oscar H %A Hofman, Albert %A Kors, Jan A %A Uitterlinden, André G %A Witteman, Jacqueline C M %A Kedenko, Lyudmyla %A Lamina, Claudia %A Oostra, Ben A %A Abecasis, Goncalo R %A Lakatta, Edward G %A Mulas, Antonella %A Orru, Marco %A Schlessinger, David %A Uda, Manuela %A Markus, Marcello R P %A Völker, Uwe %A Snieder, Harold %A Spector, Timothy D %A Arnlöv, Johan %A Lind, Lars %A Sundström, Johan %A Syvänen, Ann-Christine %A Kivimaki, Mika %A Kähönen, Mika %A Mononen, Nina %A Raitakari, Olli T %A Viikari, Jorma S %A Adamkova, Vera %A Kiechl, Stefan %A Brion, Maria %A Nicolaides, Andrew N %A Paulweber, Bernhard %A Haerting, Johannes %A Dominiczak, Anna F %A Nyberg, Fredrik %A Whincup, Peter H %A Hingorani, Aroon D %A Schott, Jean-Jacques %A Bezzina, Connie R %A Ingelsson, Erik %A Ferrucci, Luigi %A Gasparini, Paolo %A Wilson, James F %A Rudan, Igor %A Franke, Andre %A Mühleisen, Thomas W %A Pramstaller, Peter P %A Lehtimäki, Terho J %A Paterson, Andrew D %A Parsa, Afshin %A Liu, Yongmei %A van Duijn, Cornelia M %A Siscovick, David S %A Gudnason, Vilmundur %A Jamshidi, Yalda %A Salomaa, Veikko %A Felix, Stephan B %A Sanna, Serena %A Ritchie, Marylyn D %A Stricker, Bruno H %A Stefansson, Kari %A Boyer, Laurie A %A Cappola, Thomas P %A Olsen, Jesper V %A Lage, Kasper %A Schwartz, Peter J %A Kääb, Stefan %A Chakravarti, Aravinda %A Ackerman, Michael J %A Pfeufer, Arne %A de Bakker, Paul I W %A Newton-Cheh, Christopher %K Adult %K Aged %K Arrhythmias, Cardiac %K Calcium Signaling %K Death, Sudden, Cardiac %K Electrocardiography %K Female %K Genetic Predisposition to Disease %K Genome-Wide Association Study %K Genotype %K Heart Ventricles %K Humans %K Long QT Syndrome %K Male %K Middle Aged %K Myocardium %K Polymorphism, Single Nucleotide %X

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD.

%B Nat Genet %V 46 %P 826-36 %8 2014 Aug %G eng %N 8 %1 http://www.ncbi.nlm.nih.gov/pubmed/24952745?dopt=Abstract %R 10.1038/ng.3014