Six new loci associated with body mass index highlight a neuronal influence on body weight regulation

Willer, Cristen J.; Wittemann, Jacqueline; Speliotes, Elizabeth K.; Wl, McArdle; Yc, Tung; Sm, Ring; Tt, Valle; Zhao, Jing Hua; Weedon, Michael N.; Wheeler, Eleanor; Soranzo, Nicole; Loos, Ruth J. F.; Tanaka, Toshiko; Timpson, Nicholas J.; Lindgren, Cecilia M.; Heid, Iris M.; Sj, Chanock; Jackson, Anne U.; Li, Shengxu X.; Lyon, Helen N.; Papadakis, Konstantinos; McCarroll, Steven A.; Wh, Ouwehand; Smith, George Davey; Tm, Frayling; Qi, Lu; Randall, Joshua C.; Td, Spector; Sanna, Serena; Roccasecca, Rosa Maria; Traits, Consortium Genetic Investigation of ANthropometric; Scheet, Paul; Lamina, Claudia; Lettre, Guillaume; McCarroll, Steven N.; Jacobs, Leonie C.; Prokopenko, Inga; Lim, Noha; Rj, Loos; Sa, McCarroll; Burtt, N. P.; Jc, Randall; Lc, Jacobs; Mn, Weedon; Jh, Zhao; Rm, Roccasecca; Rn, Bergman; Nj, Timpson; Sa, Bingham; Im, Heid; Ll, Bonnycastle; Np, Burtt; Si, Berndt; Jm, Connell; Mr, Erdos; Kaw, Kay-Tee; Silander, Kaisa; Kb, Jacobs; Song, Kijoung; Hebebrand, Johannes; Hofman, Albert; Berndt, Sonja I.; Stephens, Jonathan; Sims, Matthew A.; Isomaa, Bo; Kt, Khaw; Elliott, Amanda L.; Stevens, Suzanne; Zillikens, Mc Carola; Waeber, Gerard; Watanabe, Richard M.; Johnson, Toby; Wallace, Chris; Stringham, Heather M.; Jacobs, Kevin B.; Jousilahti, Pekka; Waterworth, Dawn M.; Tung, Yc C. Loraine; Jovanovic, Zorica; Valle, Timo Tt; Vollenweider, Peter; Rn, Luben; Van Duijn, Cornelia M.; Watkins, Nicholas; Witteman, Jacqueline C. M.; Kraft, Peter; Vimaleswaran, Karani S.; Ridderstraale, M.; Khaw, Kay-Tee; Kuokkanen, Mikko; Pb, Munroe; Zeggini, Eleftheria; Kuusisto, Johanna; Zhai, Guangju; Laitinen, Jaana; Hn, Lyon; Luan, Jian'an; ORahilly, S.; Lakatta, Edward G.; Almgren, Peter; Mg, Rees; Mangino, Massimo; Bennett, Amanda; Luben, Robert N.; Meitinger, Thomas; Bergman, Richard N.; Mulas, Antonella; Bingham, Sheila A.; McArdle, Wendy L.; Brown, Morris; Loraine Tung, Y. C.; Ms, Sandhu; Bonnycastle, Lori Ll; Narisu, Narisu; Chines, Peter; Munroe, Patricia B.; Northstone, Kate; Lj, Scott; Coin, Lachlan; O'Rahilly, Stephen; Tuomi, Tiinamaija; Spector, Timothy D.; Ma, Sims; Ness, Andrew R.; Collins, Francis S.; Purmann, Carolin; Tuomilehto, Jaakko; Cooper, Cyrus; Connell, John M.; Uda, Manuela; Hm, Stringham; Ridderstråle, Martin; Uitterlinden, André G.; Deodhar, Parimal; Ring, Susan M.; Rees, Matthew G.; Wareham, Nicholas J.; Dennison, Elaine M.; Rm, Watanabe; Elliott, Paul; Rivadeneira, Fernando; Ks, Vimaleswaran; Jc, Witteman; Ruokonen, Aimo; Sadaf Farooqi, I.; Estrada, Karol; Erdos, Michael R.; Mc, Zillikens; Saramies, Jouko; Sandhu, Manjinder S.; Gianniny, Lauren; Mj, Caulfield; Scuteri, Angelo; Strachan, David P.; Gieger, Christian; Evans, David M.; Scott, Laura J.; Wichmann, He-Erich; Is, Farooqi; Jm, Guralnik; Guiducci, Candace; Gillson, Christopher J.; Hackett, Rachel; Mr, Järvelin; Hadley, David; Nj, Wareham; Hall, Alistair S.; Kk, Ong; Lc, Groop; Havulinna, Aki S.; Nj, Samani; Rb, Hayes; Kl, Mohlke; Peltonen, Leena; He, Wichmann; Schlessinger, David; Mi, McCarthy; Jn, Hirschhorn; Cj, Willer; Hu, Frank B.; Jarvelin, Marjo-Riitta; Ek, Speliotes; Laakso, Markku; Cm, Lindgren; Almgran, Peter; Mooser, Vincent; Ong, Ken Kk; Burtt, Noël P.; Ouwehand, Willem H.; Bertt, Noel P.; Salomaa, Veikko; Samani, Nilesh J.; Burtt, Noel L. P.; Fs, Collins; Burtt, Noel P.; Em, Dennison; Hunter, David J.; Al, Elliott; Mohlke, Karen L.; Elliot, Amanda L.; Peltonen, L.; Schlessinger, D.; Dm, Evans; Au, Jackson; McCarthy, Mark I.; Gd, Smith; Altshuler, David; Caulfield, Mark J.; Cj, Gillson; Hirschhorn, Joel N.; Chanock, Stephen J.; Farooqi, Is Sadaf; Ferrucci, Luigi; As, Hall; Guralnik, Jack M.; As, Havulinna; Hattersley, Andrew T.; Eg, Lakatta; Ar, Ness; Cm, Van Duijn; Consortium, Wellcome Trust Case Control; Carola Zillikens, M.; Control, Consortium Wellcome Trust Case; Dm, Waterworth; Deloukas, Panagiotis; At, Hattersley; Frayling, Timothy M.; Fb, Hu; Groop, Leif C.; Ag, Uitterlinden; Hayes, Richard B.; Dj, Hunter; Dp, Strachan; Boehnke, Michael; Erich Wichmann, H.; Boehnke, M.; Barroso, Inês; Bradbury, Linda M.; Abecasis, Gonçalo R.; Gr, Abecasis; Consortium, Genetic Investigation of ANthropometric Traits; Giant Consortium, Wellcome Trust Case Control

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Nicholas Timpson
Willer et al., 2008

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@article{Willer2008,
  abstract = {Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n &gt; 32,000) and followed up top signals in 14 additional cohorts (n &gt; 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P &lt; 5 x 10(-8)): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.},
  author = {Willer, Cristen J. and Wittemann, Jacqueline and Speliotes, Elizabeth K. and Wl, McArdle and Yc, Tung and Sm, Ring and Tt, Valle and Zhao, Jing Hua and Weedon, Michael N. and Wheeler, Eleanor and Soranzo, Nicole and Loos, Ruth J. F. and Tanaka, Toshiko and Timpson, Nicholas J. and Lindgren, Cecilia M. and Heid, Iris M. and Sj, Chanock and Jackson, Anne U. and Li, Shengxu X. and Lyon, Helen N. and Papadakis, Konstantinos and McCarroll, Steven A. and Wh, Ouwehand and Smith, George Davey and Tm, Frayling and Qi, Lu and Randall, Joshua C. and Td, Spector and Sanna, Serena and Roccasecca, Rosa Maria and Traits, Consortium Genetic Investigation of ANthropometric and Scheet, Paul and Lamina, Claudia and Lettre, Guillaume and McCarroll, Steven N. and Jacobs, Leonie C. and Prokopenko, Inga and Lim, Noha and Rj, Loos and Sa, McCarroll and Burtt, N. P. and Jc, Randall and Lc, Jacobs and Mn, Weedon and Jh, Zhao and Rm, Roccasecca and Rn, Bergman and Nj, Timpson and Sa, Bingham and Im, Heid and Ll, Bonnycastle and Np, Burtt and Si, Berndt and Jm, Connell and Mr, Erdos and Kaw, Kay-Tee and Silander, Kaisa and Kb, Jacobs and Song, Kijoung and Hebebrand, Johannes and Hofman, Albert and Berndt, Sonja I. and Stephens, Jonathan and Sims, Matthew A. and Isomaa, Bo and Kt, Khaw and Elliott, Amanda L. and Stevens, Suzanne and Zillikens, Mc Carola and Waeber, Gerard and Watanabe, Richard M. and Johnson, Toby and Wallace, Chris and Stringham, Heather M. and Jacobs, Kevin B. and Jousilahti, Pekka and Waterworth, Dawn M. and Tung, Yc C. Loraine and Jovanovic, Zorica and Valle, Timo Tt and Vollenweider, Peter and Rn, Luben and Van Duijn, Cornelia M. and Watkins, Nicholas and Witteman, Jacqueline C. M. and Kraft, Peter and Vimaleswaran, Karani S. and Ridderstraale, M. and Khaw, Kay-Tee and Kuokkanen, Mikko and Pb, Munroe and Zeggini, Eleftheria and Kuusisto, Johanna and Zhai, Guangju and Laitinen, Jaana and Hn, Lyon and Luan, Jian'an and ORahilly, S. and Lakatta, Edward G. and Almgren, Peter and Mg, Rees and Mangino, Massimo and Bennett, Amanda and Luben, Robert N. and Meitinger, Thomas and Bergman, Richard N. and Mulas, Antonella and Bingham, Sheila A. and McArdle, Wendy L. and Brown, Morris and Loraine Tung, Y. C. and Ms, Sandhu and Bonnycastle, Lori Ll and Narisu, Narisu and Chines, Peter and Munroe, Patricia B. and Northstone, Kate and Lj, Scott and Coin, Lachlan and O'Rahilly, Stephen and Tuomi, Tiinamaija and Spector, Timothy D. and Ma, Sims and Ness, Andrew R. and Collins, Francis S. and Purmann, Carolin and Tuomilehto, Jaakko and Cooper, Cyrus and Connell, John M. and Uda, Manuela and Hm, Stringham and Ridderstråle, Martin and Uitterlinden, André G. and Deodhar, Parimal and Ring, Susan M. and Rees, Matthew G. and Wareham, Nicholas J. and Dennison, Elaine M. and Rm, Watanabe and Elliott, Paul and Rivadeneira, Fernando and Ks, Vimaleswaran and Jc, Witteman and Ruokonen, Aimo and Sadaf Farooqi, I. and Estrada, Karol and Erdos, Michael R. and Mc, Zillikens and Saramies, Jouko and Sandhu, Manjinder S. and Gianniny, Lauren and Mj, Caulfield and Scuteri, Angelo and Strachan, David P. and Gieger, Christian and Evans, David M. and Scott, Laura J. and Wichmann, He-Erich and Is, Farooqi and Jm, Guralnik and Guiducci, Candace and Gillson, Christopher J. and Hackett, Rachel and Mr, Järvelin and Hadley, David and Nj, Wareham and Hall, Alistair S. and Kk, Ong and Lc, Groop and Havulinna, Aki S. and Nj, Samani and Rb, Hayes and Kl, Mohlke and Peltonen, Leena and He, Wichmann and Schlessinger, David and Mi, McCarthy and Jn, Hirschhorn and Cj, Willer and Hu, Frank B. and Jarvelin, Marjo-Riitta and Ek, Speliotes and Laakso, Markku and Cm, Lindgren and Almgran, Peter and Mooser, Vincent and Ong, Ken Kk and Burtt, Noël P. and Ouwehand, Willem H. and Bertt, Noel P. and Salomaa, Veikko and Samani, Nilesh J. and Burtt, Noel L. P. and Fs, Collins and Burtt, Noel P. and Em, Dennison and Hunter, David J. and Al, Elliott and Mohlke, Karen L. and Elliot, Amanda L. and Peltonen, L. and Schlessinger, D. and Dm, Evans and Au, Jackson and McCarthy, Mark I. and Gd, Smith and Altshuler, David and Caulfield, Mark J. and Cj, Gillson and Hirschhorn, Joel N. and Chanock, Stephen J. and Farooqi, Is Sadaf and Ferrucci, Luigi and As, Hall and Guralnik, Jack M. and As, Havulinna and Hattersley, Andrew T. and Eg, Lakatta and Ar, Ness and Cm, Van Duijn and Consortium, Wellcome Trust Case Control and Carola Zillikens, M. and Control, Consortium Wellcome Trust Case and Dm, Waterworth and Deloukas, Panagiotis and At, Hattersley and Frayling, Timothy M. and Fb, Hu and Groop, Leif C. and Ag, Uitterlinden and Hayes, Richard B. and Dj, Hunter and Dp, Strachan and Boehnke, Michael and Erich Wichmann, H. and Boehnke, M. and Barroso, Inês and Bradbury, Linda M. and Abecasis, Gonçalo R. and Gr, Abecasis and Consortium, Genetic Investigation of ANthropometric Traits and Giant Consortium, Wellcome Trust Case Control},
  doi = {10.1038/ng.287},
  month = {dec},
  title = {Six new loci associated with body mass index highlight a neuronal influence on body weight regulation},
  url = {http://www.ncbi.nlm.nih.gov/pubmed/19079261},
  year = {2008}
}

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Six new loci associated with body mass index highlight a neuronal influence on body weight regulation

Journal article published in 2008 by Cristen J. Willer, Jacqueline Wittemann, Elizabeth K. Speliotes, McArdle Wl, Tung Yc, Ring Sm, Valle Tt, Jing Hua Zhao, Michael N. Weedon, Eleanor Wheeler, Nicole Soranzo, Ruth J. F. Loos, Toshiko Tanaka, Nicholas J. Timpson

, Cecilia M. Lindgren and other authors. Cristen J. Willer, Jacqueline Wittemann, Elizabeth K. Speliotes, McArdle Wl, Tung Yc, Ring Sm, Valle Tt, Jing Hua Zhao, Michael N. Weedon, Eleanor Wheeler, Nicole Soranzo, Ruth J. F. Loos, Toshiko Tanaka, Nicholas J. Timpson

, Cecilia M. Lindgren, Iris M. Heid, Chanock Sj, Anne U. Jackson, Shengxu X. Li, Helen N. Lyon, Konstantinos Papadakis, Steven A. McCarroll, Ouwehand Wh, George Davey Smith, Frayling Tm, Lu Qi, Joshua C. Randall, Spector Td, Serena Sanna

, Rosa Maria Roccasecca, Consortium Genetic Investigation of ANthropometric Traits, Paul Scheet, Claudia Lamina, Guillaume Lettre, Steven N. McCarroll, Leonie C. Jacobs, Inga Prokopenko

, Noha Lim, Loos Rj, McCarroll Sa, N. P. Burtt, Randall Jc, Jacobs Lc, Weedon Mn, Zhao Jh, Roccasecca Rm, Bergman Rn, Timpson Nj, Bingham Sa, Heid Im, Bonnycastle Ll, Burtt Np, Berndt Si, Connell Jm, Erdos Mr, Kay-Tee Kaw, Kaisa Silander, Jacobs Kb, Kijoung Song, Johannes Hebebrand, Albert Hofman, Sonja I. Berndt, Jonathan Stephens, Matthew A. Sims, Bo Isomaa, Khaw Kt, Amanda L. Elliott, Suzanne Stevens, Mc Carola Zillikens, Gerard Waeber, Richard M. Watanabe, Toby Johnson

, Chris Wallace, Heather M. Stringham, Kevin B. Jacobs, Pekka Jousilahti, Dawn M. Waterworth, Yc C. Loraine Tung, Zorica Jovanovic, Timo Tt Valle, Peter Vollenweider, Luben Rn, Cornelia M. Van Duijn, Nicholas Watkins, Jacqueline C. M. Witteman, Peter Kraft, Karani S. Vimaleswaran, M. Ridderstraale, Kay-Tee Khaw, Mikko Kuokkanen, Munroe Pb, Eleftheria Zeggini

, Johanna Kuusisto, Guangju Zhai, Jaana Laitinen, Lyon Hn, Jian'an Luan, S. ORahilly, Edward G. Lakatta, Peter Almgren, Rees Mg, Massimo Mangino, Amanda Bennett, Robert N. Luben

, Thomas Meitinger, Richard N. Bergman, Antonella Mulas, Sheila A. Bingham, Wendy L. McArdle, Morris Brown, Y. C. Loraine Tung, Sandhu Ms, Lori Ll Bonnycastle, Narisu Narisu, Peter Chines, Patricia B. Munroe, Kate Northstone, Scott Lj, Lachlan Coin, Stephen O'Rahilly, Tiinamaija Tuomi, Timothy D. Spector, Sims Ma, Andrew R. Ness, Francis S. Collins, Carolin Purmann, Jaakko Tuomilehto, Cyrus Cooper, John M. Connell, Manuela Uda, Stringham Hm, Martin Ridderstråle, André G. Uitterlinden, Parimal Deodhar, Susan M. Ring, Matthew G. Rees, Nicholas J. Wareham, Elaine M. Dennison, Watanabe Rm, Paul Elliott, Fernando Rivadeneira, Vimaleswaran Ks, Witteman Jc, Aimo Ruokonen, I. Sadaf Farooqi, Karol Estrada, Michael R. Erdos, Zillikens Mc, Jouko Saramies, Manjinder S. Sandhu, Lauren Gianniny, Caulfield Mj, Angelo Scuteri, David P. Strachan, Christian Gieger

, David M. Evans, Laura J. Scott, He-Erich Wichmann, Farooqi Is, Guralnik Jm, Candace Guiducci, Christopher J. Gillson, Rachel Hackett, Järvelin Mr, David Hadley, Wareham Nj, Alistair S. Hall, Ong Kk, Groop Lc, Aki S. Havulinna, Samani Nj, Hayes Rb, Mohlke Kl, Leena Peltonen, Wichmann He, David Schlessinger, McCarthy Mi, Hirschhorn Jn, Willer Cj, Frank B. Hu, Marjo-Riitta Jarvelin, Speliotes Ek, Markku Laakso, Lindgren Cm, Peter Almgran, Vincent Mooser, Ken Kk Ong, Noël P. Burtt, Willem H. Ouwehand, Noel P. Bertt, Veikko Salomaa, Nilesh J. Samani, Noel L. P. Burtt, Collins Fs, Noel P. Burtt, Dennison Em, David J. Hunter, Elliott Al, Karen L. Mohlke, Amanda L. Elliot, L. Peltonen, D. Schlessinger, Evans Dm, Jackson Au, Mark I. McCarthy, Smith Gd, David Altshuler, Mark J. Caulfield, Gillson Cj, Joel N. Hirschhorn, Stephen J. Chanock, Is Sadaf Farooqi

, Luigi Ferrucci, Hall As, Jack M. Guralnik, Havulinna As, Andrew T. Hattersley, Lakatta Eg, Ness Ar, Van Duijn Cm, Wellcome Trust Case Control Consortium, M. Carola Zillikens, Consortium Wellcome Trust Case Control, Waterworth Dm, Panagiotis Deloukas

, Hattersley At, Timothy M. Frayling, Hu Fb, Leif C. Groop, Uitterlinden Ag, Richard B. Hayes

, Hunter Dj, Strachan Dp, Michael Boehnke, H. Erich Wichmann, M. Boehnke, Inês Barroso, Linda M. Bradbury, Gonçalo R. Abecasis, Abecasis Gr, Genetic Investigation of ANthropometric Traits Consortium, Wellcome Trust Case Control Giant Consortium

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Abstract

Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 x 10(-8)): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.

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Six new loci associated with body mass index highlight a neuronal influence on body weight regulation

Abstract