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

Title: Genetic studies of body mass index yield new insights for obesity biology
Authors: 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, Zoltán; Luan, Jian'An; Mägi, 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, Åsa K.; Karjalainen, Juha; Schmidt, Ellen M.; Absher, Devin; Amin, Najaf; Anderson, Denise; Beekman, Marian; Bolton, Jennifer L.; Bragg Gresham, Jennifer 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; Stančáková, 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; Isaacs, Aaron; Albrecht, Eva; Ärnlöv, Johan; Arscott, Gillian M.; Attwood, Antony P.; Bandinelli, Stefania; Barrett, Amy; Bas, Isabelita N.; Bellis, Claire; Bennett, Amanda J.; Berne, Christian; Blagieva, Roza; Blüher, Matthias; Böhringer, Stefan; Bonnycastle, Lori L.; Böttcher, 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 Jörgen; Grallert, Harald; Grammer, Tanja B.; Gräßler, Jürgen; Grönberg, Henrik; Groves, Christopher J.; Gusto, Gaëlle; Haessler, Jeffrey; Hall, Per; Haller, Toomas; Hallmans, Goran; Hartman, Catharina A.; Hassinen, Maija; Hayward, Caroline; Heard Costa, Nancy L.; Helmer, Quinta; Hengstenberg, Christian; Holmen, Oddgeir; Hottenga, Jouke Jan; James, Alan L.; Jeff, Janina M.; Johansson, Åsa; 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; Lindström, Jaana; Lo, Ken Sin; Lobbens, Stéphane; Lorbeer, Roberto; Lu, Yingchang; Mach, François; 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; Müller, Gabriele; Müller Nurasyid, Martina; Musk, Arthur W.; Nagaraja, Ramaiah; Nöthen, 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.; Sundström, Johan; Swertz, Morris A.; Swift, Amy J.; Syvänen, 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; Wright, Alan F.; Zhang, Qunyuan; Brennan, Eoin P.; Choi, Murim; Dastani, Zari; Drong, Alexander W.; Eriksson, Per; Franco Cereceda, Anders; Gådin, 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; Ferrières, 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.; Hyppönen, Elina; Illig, Thomas; Jacobs, Kevin B.; Jarvelin, Marjo Riitta; Jöckel, 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, Loic; Lehtimäki, Terho; Lyssenko, Valeriya; Männistö, Satu; Marette, André; 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.; Saramies, Jouko; Sarzynski, Mark A.; Schunkert, Heribert; Schwarz, Peter E. H.; Sever, Peter; Shuldiner, Alan R.; Sinisalo, Juha; Stolk, Ronald P.; Strauch, Konstantin; Tönjes, Anke; Trégouët, David Alexandre; Tremblay, Angelo; Tremoli, Elena; Virtamo, Jarmo; Vohl, Marie Claude; Völker, Uwe; Waeber, Gérard; 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, Stéphane; 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.; März, Winfried; Melbye, Mads; Metspalu, Andres; Moebus, Susanne; Munroe, Patricia B.; Njølstad, Inger; Oostra, Ben A.; Palmer, Colin N. A.; Pedersen, Nancy L.; Perola, Markus; Pérusse, 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, Unnur; Stumvoll, Michael; Tuomilehto, Jaakko; Uitterlinden, André 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 Duijn, Cornelia M.; Abecasis, Gonçalo R.; Franke, Lude; Frayling, Timothy M.; Mccarthy, Mark I.; Visscher, Peter M.; Scherag, André; Willer, Cristen J.; Boehnke, Michael; Mohlke, Karen L.; Lindgren, Cecilia M.; Beckmann, Jacques S.; Barroso, Inɥs; North, Kari E.; Ingelsson, Erik; Hirschhorn, Joel N.; Loos, Ruth J. F.; Speliotes, Elizabeth K.; Deloukas P; Kanoni S; Willenborg C; Farrall M; Assimes TL; Thompson JR; Ingelsson E; Saleheen D; Erdmann J; Goldstein BA; Stirrups K; König IR; Cazier JB; Johansson Å; Hall AS; Lee JY; Willer CJ; Chambers JC; Esko T; Folkersen L; Goel A; Grundberg E; Havulinna AS; Ho WK; Hopewell JC; Eriksson N; Kleber ME; Kristiansson K; Lundmark P; Lyytikäinen LP; Rafelt S; Shungin D; Strawbridge RJ; Thorleifsson G; Tikkanen E; Van Zuydam N; Voight BF; Waite LL; Zhang W; Ziegler A; Absher D; Altshuler D; Balmforth AJ; Barroso I; Braund PS; Burgdorf C; Claudi Boehm S; Cox D; Dimitriou M; Do R; Doney AS; El Mokhtari N; Eriksson P; Fischer K; Fontanillas P; Franco Cereceda A; Gigante B; Groop L; Gustafsson S; Hager J; Hallmans G; Han BG; Hunt SE; Kang HM; Illig T; Kessler T; Knowles JW; Kolovou G; Kuusisto J; Langenberg C; Langford C; Leander K; Lokki ML; Lundmark A; McCarthy MI; Meisinger C; Melander O; Mihailov E; Maouche S; Morris AD; Müller Nurasyid M; Nikus K; Peden JF; Rayner NW; Rasheed A; Rosinger S; Rubin D; Rumpf MP; Schäfer A; Sivananthan M; Song C; Stewart AF; Tan ST; Thorgeirsson G; van der Schoot CE; Wagner PJ; Wells GA; Wild PS; Tsun Po Y; Amouyel P; Arveiler D; Basart H; Boehnke M; Boerwinkle E; Brambilla P; Cambien F; Cupples AL; de Faire U; Dehghan A; Diemert P; Epstein SE; Evans A; Ferrario MM; Ferrières J; Gauguier D; Go AS; Goodall AH; Gudnason V; Hazen SL; Holm H; Iribarren C; Jang Y; Kähönen M; Kee F; Kim HS; Klopp N; Koenig W; Kratzer W; Kuulasmaa K; Laakso M; Laaksonen R; Lind L; Ouwehand WH; Parish S; Park JE; Pedersen NL; Peters A; Quertermous T; Rader DJ; Salomaa V; Schadt E; Shah SH; Sinisalo J; Stark K; Stefansson K; Trégouët DA; Virtamo J; Wallentin L; Wareham N; Zimmermann ME; Nieminen MS; Hengstenberg C; Sandhu MS; Pastinen T; Syvänen AC; Hovingh GK; Dedoussis G; Franks PW; Lehtimäki T; Metspalu A; Zalloua PA; Siegbahn A; Schreiber S; Ripatti S; Blankenberg SS; Perola M; Clarke R; Boehm BO; O'Donnell C; Reilly MP; März W; Collins R; Kathiresan S; Hamsten A; Kooner JS; Thorsteinsdottir U; Danesh J; Palmer CN; Roberts R; Watkins H; Schunkert H; Samani NJ; Pattaro C; Köttgen A; Teumer A; Garnaas M; Böger CA; Fuchsberger C; Olden M; Chen MH; Tin A; Taliun D; Li M; Gao X; Gorski M; Yang Q; Hundertmark C; Foster MC; O'Seaghdha CM; Glazer N; Isaacs A; Liu CT; Smith AV; O'Connell JR; Struchalin M; Tanaka T; Li G; Johnson AD; Gierman HJ; Feitosa M; Hwang SJ; Atkinson EJ; Lohman K; Cornelis MC; Tönjes A; Chouraki V; Holliday EG; Sorice R; Kutalik Z; Deshmukh H; Ulivi S; Chu AY; Murgia F; Trompet S; Imboden M; Kollerits B; Pistis G; Harris TB; Launer LJ; Aspelund T; Eiriksdottir G; Mitchell BD; Schmidt H; Cavalieri M; Rao M; Hu FB; Demirkan A; Oostra BA; de Andrade M; Turner ST; Ding J; Andrews JS; Freedman BI; Döring A; Wichmann HE; Kolcic I; Zemunik T; Boban M; Minelli C; Wheeler HE; Igl W; Zaboli G; Wild SH; Wright AF; Campbell H; Ellinghaus D; Nöthlings U; Jacobs G; Biffar R; Endlich K; Ernst F; Homuth G; Kroemer HK; Nauck M; Stracke S; Völker U; Völzke H; Kovacs P; Stumvoll M; Mägi R; Hofman A; Uitterlinden AG; Rivadeneira F; Aulchenko YS; Polasek O; Hastie N; Vitart V; Helmer C; Wang JJ; Ruggiero D; Bergmann S; Viikari J; Nikopensius T; Province M; Ketkar S; Colhoun H; Doney A; Robino A; Giulianini F; Krämer BK; Portas L; Ford I; Buckley BM; Adam M; Thun GA; Paulweber B; Haun M; Sala C; Metzger M; Mitchell P; Ciullo M; Kim SK; Vollenweider P; Raitakari O; Palmer C; Gasparini P; Pirastu M; Jukema J; Probst Hensch NM; Kronenberg F; Toniolo D; Shuldiner AR; Coresh J; Schmidt R; Ferrucci L; Siscovick DS; van Duijn CM; Borecki I; Kardia SL; Liu Y; Curhan GC; Rudan I; Gyllensten U; Wilson JF; Franke A; Pramstaller PP; Rettig R; Prokopenko I; Witteman JC; Hayward C; Ridker P; Parsa A; Bochud M; Heid IM; Goessling W; Chasman DI; Kao W; Fox CS; de Boer IH; Glazer NL; Peralta CA; Luan J; Zhao JH; Akylbekova E; Kramer H; van der Harst P; Arking DE; Franceschini N; Egan J; Hernandez D; Reilly M; Townsend RR; Lumley T; 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Contributors: 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, Zoltán; Luan, Jian'An; Mägi, 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, Åsa K.; Karjalainen, Juha; Schmidt, Ellen M.; Absher, Devin; Amin, Najaf; Anderson, Denise; Beekman, Marian; Bolton, Jennifer L.; Bragg Gresham, Jennifer 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; Stančáková, 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; Isaacs, Aaron; Albrecht, Eva; Ärnlöv, Johan; Arscott, Gillian M.; Attwood, Antony P.; Bandinelli, Stefania; Barrett, Amy; Bas, Isabelita N.; Bellis, Claire; Bennett, Amanda J.; Berne, Christian; Blagieva, Roza; Blüher, Matthia; Böhringer, Stefan; Bonnycastle, Lori L.; Böttcher, 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
Publication Year: 2015
Collection: IRIS UNIPV (Università degli studi di Pavia)
Subject Terms: Adipogenesi; Adiposity; Age Factor; Continental Population Group; Energy Metabolism; Europe; Female; Genetic Predisposition to Disease; Glutamic Acid; Human; Insulin; Male; Obesity; Polymorphism; Single Nucleotide; Quantitative Trait Loci; Synapse; Body Mass Index; Genome-Wide Association Study; Medicine (all); Multidisciplinary
Description: 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
Document Type: article in journal/newspaper
File Description: STAMPA
Language: English
Relation: info:eu-repo/semantics/altIdentifier/pmid/25673413; info:eu-repo/semantics/altIdentifier/wos/WOS:000349190300031; volume:518; issue:7538; firstpage:197; lastpage:206; numberofpages:10; journal:NATURE; http://hdl.handle.net/11571/1182207; http://www.nature.com/nature/index.html
DOI: 10.1038/nature14177
Availability: http://hdl.handle.net/11571/1182207; https://doi.org/10.1038/nature14177; http://www.nature.com/nature/index.html
Accession Number: edsbas.75165B0B
Database: BASE