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

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Locke, AE (Locke, Adam E.); Kahali, B (Kahali, Bratati); Berndt, SI (Berndt, Sonja I.); Justice, AE (Justice, Anne E.); Pers, TH (Pers, Tune H.); Felix, R (Day, Felix R.);

Powell, C (Powell, Corey); Vedantam, S (Vedantam, Sailaja); Buchkovich, ML (Buchkovich, Martin L.); Yang, J (Yang, Jian); Croteau-Chonka, DC (Croteau-Chonka, Damien C.); Esko, T (Esko, Tonu); Fall, T (Fall, Tove); Ferreira, T (Ferreira, Teresa);

Gustafsson, S (Gustafsson, Stefan); Kutalik, Z (Kutalik, Zoltan); Luan, JA (Luan, Jian'an); Magi, R (Maegi, Reedik); Randall, JC (Randall, Joshua C.); Winkler, TW

(Winkler, Thomas W.); Wood, AR (Wood, Andrew R.); Workalemahu, T (Workalemahu, Tsegaselassie); Faul, JD (Faul, Jessica D.); Smith, JA (Smith, Jennifer A.); Zhao, JH (Zhao, Jing Hua); Zhao, W (Zhao, Wei); Chen, J (Chen, Jin);

Fehrmann, R (Fehrmann, Rudolf); Hedman, AK (Hedman, Asa K.); Karjalainen, J (Karjalainen, Juha); Schmidt, EM (Schmidt, Ellen M.); Absher, D (Absher, Devin);

Amin, N (Amin, Najaf); Anderson, D (Anderson, Denise); Beekman, M (Beekman, Marian); Bolton, JL (Bolton, Jennifer L.); Bragg-Gresham, L (Bragg-Gresham, L.);

Buyske, S (Buyske, Steven); Demirkan, A (Demirkan, Ayse); Deng, GH (Deng, Guohong); Ehret, GB (Ehret, Georg B.); Feenstra, B (Feenstra, Bjarke); Feitosa, MF

(Feitosa, Mary F.); Fischer, K (Fischer, Krista); Goel, A (Goel, Anuj); Gong, J (Gong, Jian); Jackson, AU (Jackson, Anne U.); Kanoni, S (Kanoni, Stavroula); Kleber, ME

(Kleber, Marcus E.); Kristiansson, K (Kristiansson, Kati); Lim, U (Lim, Unhee);

Lotay, V (Lotay, Vaneet); Mangino, M (Mangino, Massimo); Leach, IM (Leach, Irene Mateo); Medina-Gomez, C (Medina-Gomez, Carolina); Medland, SE (Medland, Sarah

E.); Nalls, MA (Nalls, Michael A.); Palmer, CD (Palmer, Cameron D.); Pasko, D (Pasko, Dorota); Pechlivanis, S (Pechlivanis, Sonali); Peters, MJ (Peters, Marjolein J.); Prokopenko, I (Prokopenko, Inga); Shungin, D (Shungin, Dmitry); Stancakova, A (Stancakova, Alena); Strawbridge, RJ (Strawbridge, Rona J.); Sung, YJ (Sung, Yun

Ju); Tanaka, T (Tanaka, Toshiko); Teumer, A (Teumer, Alexander); Trompet, S (Trompet, Stella); van der Laan, SW (van der Laan, Sander W.); van Settee, J (van Settee, Jessica); Van Vliet-Ostaptchouk, JV (Van Vliet-Ostaptchouk, Jana V.); Wang, ZM (Wang, Zhaoming); Yengo, L (Yengo, Loic); Zhang, WH (Zhang, Weihua); Isaacs, A (Isaacs, Aaron); Albrecht, E (Albrecht, Eva); Arnlov, J (Arnlov, Johan); Arscott, GM

(Arscott, Gillian M.); Attwood, AP (Attwood, Antony P.); Bandinelli, S (Bandinelli, Stefania); Barrett, A (Barrett, Amy); Bas, IN (Bas, Isabelita N.); Bellis, C (Bellis, Claire); Bennett, AJ (Bennett, Amanda J.); Berne, C (Berne, Christian); Blagieva, R (Blagieva, Roza); Bluher, M (Blueher, Matthias); Bohringer, S (Bohringer, Stefan);

Bonnycastle, LL (Bonnycastle, Lori L.); Bottcher, Y (Boettcher, Yvonne); Boyd, HA (Boyd, Heather A.); Bruinenberg, M (Bruinenberg, Marcel);

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Caspersen, IH (Caspersen, Ida H.); Chen, YD (Chen, Yii-Der Ida); Clarke, R (Clarke, Robert); Daw, EW (Daw, E. Warwick); de Craen, AJM (de Craen, Anton J. M.);

Delgado, G (Delgado, Graciela); Dimitriou, M (Dimitriou, Maria); Doney, ASF (Doney, Alex S. F.); Eklund, N (Eklund, Niina); Estrada, K (Estrada, Karol); Eury, E

(Eury, Elodie); Folkersen, L (Folkersen, Lasse); Fraser, RM (Fraser, Ross M.);

Garcia, ME (Garcia, Melissa E.); Geller, F (Geller, Frank); Giedraitis, V (Giedraitis, Vilmantas); Gigante, B (Gigante, Bruna); Go, AS (Go, Alan S.); Golay, A (Golay, Alain); Goodall, AH (Goodall, Alison H.); Gordon, SD (Gordon, Scott D.); Gorski, M (Gorski, Mathias); Grabe, HJ (Grabe, Hans-Joergen); Grallert, H (Grallert, Harald);

Grammer, TB (Grammer, Tanja B.); Grassler, J (Graessler, Jurgen); Gronberg, H (Gronberg, Henrik); Groves, CJ (Groves, Christopher J.); Gusto, G (Gusto, Gaeelle);

Haessler, J (Haessler, Jeffrey); Hall, P (Hall, Per); Haller, T (Haller, Toomas);

Hallmans, G (Hallmans, Goran); Hartman, CA (Hartman, Catharina A.); Hassinen, M (Hassinen, Maija); Hayward, C (Hayward, Caroline); Heard-Costa, NL (Heard-Costa, Nancy L.); Helmer, Q (Helmer, Qinta); Hengstenberg, C (Hengstenberg, Christian);

Holmen, O (Holmen, Oddgeir); Hottenga, JJ (Hottenga, Jouke-Jan); James, AL (James, Alan L.); Jeff, JM (Jeff, Janina M.); Johansson, A (Johansson, Asa); Jolley, J (Jolley, Jennifer); Juliusdottir, T (Juliusdottir, Thorhildur); Kinnunen, L (Kinnunen,

Leena); Koenig, W (Koenig, Wolfgang); Koskenvuo, M (Koskenvuo, Markku);

Kratzer, W (Kratzer, Wolfgang); Laitinen, J (Laitinen, Jaana); Lamina, C (Lamina, Claudia); Leander, K (Leander, Karin); Lee, NR (Lee, Nanette R.); Lichtner, P (Lichtner, Peter); Lind, L (Lind, Lars); Lindstrom, J (Lindstrom, Jaana); Lo, KS (Lo,

Ken Sin); Lobbens, S (Lobbens, Stephane); Lorbeer, R (Lorbeer, Roberto); Lu, YC (Lu, Yingchang); Mach, F (Mach, Francois); Magnusson, PKE (Magnusson, Patrik K.

E.); Mahajan, A (Mahajan, Anubha); McArdle, WL (McArdle, Wendy L.); McLachlan, S (McLachlan, Stela); Menni, C (Menni, Cristina); Merger, S (Merger, Sigrun);

Mihailov, E (Mihailov, Evelin); Milani, L (Milani, Lili); Moayyeri, A (Moayyeri, Alireza); Monda, KL (Monda, Keri L.); Morken, MA (Morken, Mario A.); Mulas, A (Mulas, Antonella); Muller, G (Mueller, Gabriele); Muller-Nurasyid, M (Mueller-

Nurasyid, Martina); Musk, AW (Musk, Arthur W.); Nagaraja, R (Nagaraja, Ramaiah); Nothen, MM (Noethen, Markus M.); Nolte, IM (Nolte, Ilja M.); Pilz, S (Pilz,

Stefan); Rayner, NW (Rayner, Nigel W.); Renstrom, F (Renstrom, Frida); Rettig, R (Rettig, Rainer); Ried, JS (Ried, Janina S.); Ripke, S (Ripke, Stephan); Robertson, NR

(Robertson, Neil R.); Rose, LM (Rose, Lynda M.); Sanna, S (Sanna, Serena);

Scharnagl, H (Scharnagl, Hubert); Scholtens, S (Scholtens, Salome); Schumacher, FR (Schumacher, Fredrick R.); Scott, WR (Scott, William R.); Seufferlein, T (Seufferlein, Thomas); Shi, JX (Shi, Jianxin); Smith, AV (Smith, Albert Vernon);

Smolonska, J (Smolonska, Joanna); Stanton, AV (Stanton, Alice V.);

Steinthorsdottir, V (Steinthorsdottir, Valgerdur); Stirrups, K (Stirrups, Kathleen);

Stringham, HM (Stringham, Heather M.); Sundstrom, J (Sundstrom, Johan); Swertz, MA (Swertz, Morris A.); Swift, AJ (Swift, Amy J.); Syvanen, AC (Syvanen, Ann- Christine); Tan, ST (Tan, Sian-Tsung); Tayo, BO (Tayo, Bamidele O.); Thorand, B

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(Thorand, Barbara); Thorleifsson, G (Thorleifsson, Gudmar); Tyrer, JP (Tyrer, Jonathan P.); Uh, HW (Uh, Hae-Won); Vandenput, L (Vandenput, Liesbeth);

Verhulst, FC (Verhulst, Frank C.); Vermeulen, SH (Vermeulen, Sita H.); Verweij, N (Verweij, Niek); Vonk, JM (Vonk, Judith M.); Waite, LL (Waite, Lindsay L.); Warren,

HR (Warren, Helen R.); Waterworth, D (Waterworth, Dawn); Weedon, MN (Weedon, Michael N.); Wilkens, LR (Wilkens, Lynne R.); Willenborg, C (Willenborg, Christina); Wilsgaard, T (Wilsgaard, Tom); Wojczynski, MK (Wojczynski, Mary K.);

Wong, A (Wong, Andrew); Wrightl, AF (Wrightl, Alan F.); Zhang, QY (Zhang, Qunyuan); Brennan, EP (Brennan, Eoin P.); Choi, M (Choi, Murim); Dastani, Z (Dastani, Zari); Drong, AW (Drong, Alexander W.); Eriksson, P (Eriksson, Per);

Franco-Cereceda, A (Franco-Cereceda, Anders); Gadin, JR (Gadin, Jesper R.);

Gharavi, AG (Gharavi, Ali G.); Goddard, ME (Goddard, Michael E.); Handsaker, RE (Handsaker, Robert E.); Huang, JY (Huang, Jinyan); Karpe, F (Karpe, Fredrik);

Kathiresan, S (Kathiresan, Sekar); Keildson, S (Keildson, Sarah); Kiryluk, K (Kiryluk, Krzysztof); Kubo, M (Kubo, Michiaki); Lee, JY (Lee, Jong-Young); Liang, L (Liang, Liming); Lifton, RP (Lifton, Richard P.); Ma, BS (Ma, Baoshan); McCarroll, SA

(McCarroll, Steven A.); McKnight, AJ (McKnight, Amy J.); Min, JL (Min, Josine L.);

Moffatt, MF (Moffatt, Miriam F.); Montgomery, GW (Montgomery, Grant W.);

Murabito, JM (Murabito, Joanne M.); Nicholson, G (Nicholson, George); Nyholt, DR (Nyholt, Dale R.); Okada, Y (Okada, Yukinori); Perry, JRB (Perry, John R. B.);

Dorajoo, R (Dorajoo, Rajkumar); Reinmaa, E (Reinmaa, Eva); Salem, RM (Salem, Rany M.); Sandholm, N (Sandholm, Niina); Scott, RA (Scott, Robert A.); Stolk, L (Stolk, Lisette); Takahashi, A (Takahashi, Atsushi); Tanaka, T (Tanaka, Toshihiro);

van 't Hooft, FM (van 't Hooft, Ferdinand M.); Vinkhuyzen, AAE (Vinkhuyzen, Anna A. E.); Westra, HJ (Westra, Harm-Jan); Zheng, W (Zheng, Wei); Zondervan, KT

(Zondervan, Krina T.); Heath, AC (Heath, Andrew C.); Arveiler, D (Arveiler, Dominique); Bakker, SJL (Bakker, Stephan J. L.); Beilby, J (Beilby, John); Bergman,

RN (Bergman, Richard N.); Blangero, J (Blangero, John); Bovet, P (Bovet, Pascal);

Campbell, H (Campbell, Harry); Caulfield, MJ (Caulfield, Mark J.); Cesana, G (Cesana, Giancarlo); Chakravarti, A (Chakravarti, Aravinda); Chasman, DI (Chasman, Daniel I.); Chines, PS (Chines, Peter S.); Collins, FS (Collins, Francis S.);

Crawford, DC (Crawford, Dana C.); Cupples, LA (Cupples, L. Adrienne); Cusi, D (Cusi, Daniele); Danesh, J (Danesh, John); de Faire, U (de Faire, Ulf); den Ruijter,

HM (den Ruijter, Hester M.); Dominiczak, AF (Dominiczak, Anna F.); Erbel, R (Erbel, Raimund); Erdmann, J (Erdmann, Jeanette); Eriksson, JG (Eriksson, Johan

G.); Farrall, M (Farrall, Martin); Felix, SB (Felix, Stephan B.); Ferrannini, E (Ferrannini, Ele); Ferrieres, J (Ferrieres, Jean); Ford, I (Ford, Ian); Forouhi, NG (Forouhi, Nita G.); Forrester, T (Forrester, Terrence); Franco, OH (Franco, Oscar H.); Gansevoort, RT (Gansevoort, Ron T.); Gejman, PV (Gejman, Pablo V.); Gieger, C

(Gieger, Christian); Gottesman, O (Gottesman, Omri); Gudnason, V (Gudnason, Vilmundur); Gyllensten, U (Gyllensten, Ulf); Hall, AS (Hall, Alistair S.); Harris, TB

(Harris, Tamara B.); Hattersley, AT (Hattersley, Andrew T.); Hicks, AA (Hicks,

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Andrew A.); Hindorff, LA (Hindorff, Lucia A.); Hingorani, AD (Hingorani, Aroon D.);

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JJP (Kastelein, John J. P.); Keinanen-Kiukaanniemi, SM (Keinanen-Kiukaanniemi, Sirkka M.); Kiemeney, LA (Kiemeney, Lambertus A.); Knekt, P (Knekt, Paul);

Kooner, JS (Kooner, Jaspal S.); Kooperberg, C (Kooperberg, Charles); Kovacs, P (Kovacs, Peter); Kraja, AT (Kraja, Aldi T.); Kumari, M (Kumari, Meena); Kuusisto, J

(Kuusisto, Johanna); Lakka, TA (Lakka, Timo A.); Langenberg, C (Langenberg, Claudia); Le Marchand, L (Le Marchand, Laic); Lehtimaki, T (Lehtimaki, Terho);

Lyssenko, V (Lyssenko, Valeriya); Mannisto, S (Mannisto, Satu); Marette, A (Marette, Andre); Matise, TC (Matise, Tara C.); McKenzie, CA (McKenzie, Colin A.);

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(Pasterkamp, Gerard); Peden, JF (Peden, John F.); Peters, A (Peters, Annette);

Postma, DS (Postma, Dirkje S.); Pramstaller, PP (Pramstaller, Peter P.); Price, JF (Price, Jackie F.); Qi, L (Qi, Lu); Raitakari, OT (Raitakari, Olli T.); Rankinen, T (Rankinen, Tuomo); Rao, DC (Rao, D. C.); Rice, TK (Rice, Treva K.); Ridker, PM (Ridker, Paul M.); Rioux, JD (Rioux, John D.); Ritchie, MD (Ritchie, Marylyn D.);

Rudan, I (Rudan, Igor); Salomaa, V (Salomaa, Veikko); Samani, NJ (Samani, Nilesh J.); Saramines, J (Saramines, Jouko); Sarzynski, MA (Sarzynski, Mark A.);

Schunkert, H (Schunkert, Heribert); Schwarz, PEH (Schwarz, Peter E. H.); Sever, P (Sever, Peter); Shuldiner, AR (Shuldiner, Alan R.); Sinisalo, J (Sinisalo, Juha); Stolk,

RP (Stolk, Ronald P.); Strauch, K (Strauch, Konstantin); Tonjes, A (Toenjes, Anke);

Tregouet, DA (Tregouet, David-Alexandre); Tremblay, A (Tremblay, Angelo);

Tremoli, E (Tremoli, Elena); Virtamo, J (Virtamo, Jarmo); Vohl, MC (Vohl, Marie- Claude); Volker, U (Voelker, Uwe); Waeber, G (Waeber, Gerard); Willemsen, G

(Willemsen, Gonneke); Witteman, JC (Witteman, Jacqueline C.); Zillikens, MC (Zillikens, M. Carola); Adair, LS (Adair, Linda S.); Amouyel, P (Amouyel, Philippe);

Asselbergs, FW (Asselbergs, Folkert W.); Assimes, TL (Assimes, Themistocles L.);

Bochud, M (Bochud, Murielle); Boehm, BO (Boehm, Bernhard O.); Boerwinkle, E (Boerwinkle, Eric); Bornstein, SR (Bornstein, Stefan R.); Bottinger, EP (Bottinger,

Erwin P.); Bouchard, C (Bouchard, Claude); Cauchi, S (Cauchi, Stephane);

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Froguel, P (Froguel, Philippe); Groop, LC (Groop, Leif C.); Haiman, CA (Haiman,

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Christopher A.); Hamsten, A (Hamsten, Anders); Hui, JN (Hui, Jennie); Hunter, DJ (Hunter, David J.); Hveem, K (Hveem, Kristian); Kaplan, RC (Kaplan, Robert C.);

Kivimaki, M (Kivimaki, Mika); Kuh, D (Kuh, Diana); Laakso, M (Laakso, Markku);

Liu, YM (Liu, Yongmei); Martin, NG (Martin, Nicholas G.); Marz, W (Maerz, Winfried); Melbve, M (Melbve, Mads); Metspalu, A (Metspalu, Andres); Moebus, S (Moebus, Susanne); Munroe, PB (Munroe, Patricia B.); Njolstad, I (Njolstad, Inger);

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N (Sattar, Naveed); Schadt, EE (Schadt, Eric E.); Schlessinger, D (Schlessinger, David); Slagboom, PE (Slagboom, P. Eline); Snieder, H (Snieder, Harold); Spector, TD (Spector, Tim D.); Thorsteinsdottir, UR (Thorsteinsdottir, Unnu R.); Stumvoll,

M (Stumvoll, Michael); Tuomilehto, J (Tuomilehto, Jaakko); Uitterlinden, AG (Uitterlinden, Andre G.); Uusitupa, M (Uusitupa, Matti); van der Harst, P (van der Harst, Pim); Walker, M (Walker, Mark); Wallaschofski, H (Wallaschofski, Henri);

Wareham, NJ (Wareham, Nicholas J.); Watkins, H (Watkins, Hugh); Weir, DR (Weir, David R.); Wichmann, HE (Wichmann, H-Erich); Wilson, JF (Wilson, James F.);

Zanen, P (Zanen, Pieter); Borecki, IB (Borecki, Ingrid B.); Deloukas, P (Deloukas, Panos); Fox, CS (Fox, Caroline S.); Heid, IM (Heid, Iris M.); O'Connell, JR (O'Connell, Jeffrey R.); Strachan, DP (Strachan, David P.); Stefansson, K (Stefansson, Kari); van Duijri, CM (van Duijri, Cornelia M.); Abecasis, GR (Abecasis, Goncalo R.); Franke, L

(Franke, Lude); Frayling, TM (Frayling, Timothy M.); McCarthy, MI (McCarthy, Mark I.); Visscher, PM (Visscher, Peter M.); Scherag, A (Scherag, Andre); Willer, CJ

(Willer, Cristen J.); Boehnke, M (Boehnke, Michael); Mohlke, KL (Mohlke, Karen L.); Lindgren, CM (Lindgren, Cecilia M.); Beckmann, JS (Beckmann, Jacques S.);

Barroso, I (Barroso, Ines); North, KE (North, Kari E.); Ingelsson, E (Ingelsson, Erik);

Hirschhorn, JN (Hirschhorn, Joel N.); Loos, RJF (Loos, Ruth J. F.); Speliotes, EK (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.

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Sources : NATURE

ISO Source Abbrev : Nature Impact Factor : 38.138

Year : 2015

Volume : 518

Issue : 7538

Pages : 197-U401

DOI : 10.1016/j.icheatmasstransfer.2011.12.002 Cited reference count : 29

Languge : English

Document Type : Article

Reprint Address : Speliotes, EK (reprint author), Univ Michigan, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA.

Publisher : NATURE PUBLISHING GROUP Web of Science Categories : Multidisciplinary Sciences

Research Areas : Science & Technology - Other Topics

Faculty Name : Center of Princess Al-Jawhara for Excellence in Research of Hereditary Disorders

DSR No. : 7109

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17. Genome-wide meta-analysis identifies six novel loci associated

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