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

CJ Willer; EK Speliotes; RJ Loos; S Li; CM Lindgren; IM Heid; SI Berndt; Al Elliott; AU Jackson; C Lamina; G Lettre; N Lim; HN Lyon; SA McCarroll; K Papadakis; L Qi; JC Randall; Rm Roccasecca; S Sanna; P Scheet; MN Weedon; E Wheeler; JH Zhao; LC Jacobs; I Prokopenko; N Soranzo; T Tanaka; Nicholas John Timpson; P Almgren; A Bennett; RN Bergman; SA Bingham; LL Bonnycastle; M Brown; NP Burtt; P Chines; L Coin; FS Collins; JM Connell; C Cooper; G Davey Smith; EM Dennison; P Deodhar; P Elliott; MR Erdos; K Estrada; DM Evans; L Gianniny; C Gieger; CJ Gillson; C Guiducci; R Hackett; D Hadley; AS Hall; AS Havulinna; J Hebebrand; A Hofman; B Isomaa; KB Jacobs; T Johnson; P Jousilahti; Z Jovanovic; KT Khaw; P Kraft; M Kuokkanen; J Kuusisto; J Laitinen; EG Lakatta; J Luan; RN Luben; M Mangino; WL McArdle; T Meitinger; A Mulas; PB Munroe; N Narisu; A Ness; K Northstone; S O'Rahilly; C Purmann; MG Rees; M Ridderstråle; SM Ring; F Rivadeneira; A Ruokonen; MS Sandhu; J Saramies; LJ Scott; A Scuteri; K Silander; MA Sims; K Song; J Stephens; S Stevens; HM Stringham; YC Tung; TT Valle; CM Van Duijn; KS Vimaleswaran; P Vollenweider; G Waeber; C Wallace; RM Watanabe; DM Waterworth; N Watkins; Consortium Wellcome Trust Case Control; JC Witteman; E Zeggini; G Zhai; MC Zillikens; D Altshuler; MJ Caulfield; SJ Chanock; IS Farooqi; L Ferrucci; JM Guralnik; AT Hattersley; FB Hu; MR Jarvelin; M Laakso; V Mooser; KK Ong; WH Ouwehand; V Salomaa; NJ Samani; TD Spector; T Tuomi; J Tuomilehto; M Uda; AG Uitterlinden; NJ Wareham; P Deloukas; TM Frayling; LC Groop; RB Hayes; DJ Hunter; KL Mohlke; L Peltonen; D Schlessinger; DP Strachan; HE Wichmann; MI McCarthy; M Boehnke; L Peltonen; D Schlessinger; DP Strachan; HE Wichmann; MI McCarthy; M Boehnke; I Barroso; GR Abecasis; JN Hirschhorn; Consortium Genetic Investigation of ANthropometric Traits

doi:10.1038/ng.287

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

CJ Willer, EK Speliotes, RJ Loos, S Li, CM Lindgren, IM Heid, SI Berndt, Al Elliott, AU Jackson, C Lamina, G Lettre, N Lim, HN Lyon, SA McCarroll, K Papadakis, L Qi, JC Randall, Rm Roccasecca, S Sanna, P ScheetMN Weedon, E Wheeler, JH Zhao, LC Jacobs, I Prokopenko, N Soranzo, T Tanaka, Nicholas John Timpson, P Almgren, A Bennett, RN Bergman, SA Bingham, LL Bonnycastle, M Brown, NP Burtt, P Chines, L Coin, FS Collins, JM Connell, C Cooper, G Davey Smith, EM Dennison, P Deodhar, P Elliott, MR Erdos, K Estrada, DM Evans, L Gianniny, C Gieger, CJ Gillson, C Guiducci, R Hackett, D Hadley, AS Hall, AS Havulinna, J Hebebrand, A Hofman, B Isomaa, KB Jacobs, T Johnson, P Jousilahti, Z Jovanovic, KT Khaw, P Kraft, M Kuokkanen, J Kuusisto, J Laitinen, EG Lakatta, J Luan, RN Luben, M Mangino, WL McArdle, T Meitinger, A Mulas, PB Munroe, N Narisu, A Ness, K Northstone, S O'Rahilly, C Purmann, MG Rees, M Ridderstråle, SM Ring, F Rivadeneira, A Ruokonen, MS Sandhu, J Saramies, LJ Scott, A Scuteri, K Silander, MA Sims, K Song, J Stephens, S Stevens, HM Stringham, YC Tung, TT Valle, CM Van Duijn, KS Vimaleswaran, P Vollenweider, G Waeber, C Wallace, RM Watanabe, DM Waterworth, N Watkins, Consortium Wellcome Trust Case Control, JC Witteman, E Zeggini, G Zhai, MC Zillikens, D Altshuler, MJ Caulfield, SJ Chanock, IS Farooqi, L Ferrucci, JM Guralnik, AT Hattersley, FB Hu, MR Jarvelin, M Laakso, V Mooser, KK Ong, WH Ouwehand, V Salomaa, NJ Samani, TD Spector, T Tuomi, J Tuomilehto, M Uda, AG Uitterlinden, NJ Wareham, P Deloukas, TM Frayling, LC Groop, RB Hayes, DJ Hunter, KL Mohlke, L Peltonen, D Schlessinger, DP Strachan, HE Wichmann, MI McCarthy, M Boehnke, L Peltonen, D Schlessinger, DP Strachan, HE Wichmann, MI McCarthy, M Boehnke, I Barroso, GR Abecasis, JN Hirschhorn, Consortium Genetic Investigation of ANthropometric Traits

Research output: Contribution to journal › Article (Academic Journal) › peer-review

1330 Citations (Scopus)

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.

Original language	English
Pages (from-to)	25-34
Number of pages	9
Journal	Nature Genetics
Volume	41
Issue number	1
DOIs	https://doi.org/10.1038/ng.287
Publication status	Published - 2009

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Publisher: Nature Pub. Co

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10.1038/ng.287

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Willer, CJ., Speliotes, EK., Loos, RJ., Li, S., Lindgren, CM., Heid, IM., Berndt, SI., Elliott, A., Jackson, AU., Lamina, C., Lettre, G., Lim, N., Lyon, HN., McCarroll, SA., Papadakis, K., Qi, L., Randall, JC., Roccasecca, R., Sanna, S., ... Genetic Investigation of ANthropometric Traits, C. (2009). Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nature Genetics, 41(1), 25-34. https://doi.org/10.1038/ng.287

Willer, CJ ; Speliotes, EK ; Loos, RJ ; Li, S ; Lindgren, CM ; Heid, IM ; Berndt, SI ; Elliott, Al ; Jackson, AU ; Lamina, C ; Lettre, G ; Lim, N ; Lyon, HN ; McCarroll, SA ; Papadakis, K ; Qi, L ; Randall, JC ; Roccasecca, Rm ; Sanna, S ; Scheet, P ; Weedon, MN ; Wheeler, E ; Zhao, JH ; Jacobs, LC ; Prokopenko, I ; Soranzo, N ; Tanaka, T ; Timpson, Nicholas John ; Almgren, P ; Bennett, A ; Bergman, RN ; Bingham, SA ; Bonnycastle, LL ; Brown, M ; Burtt, NP ; Chines, P ; Coin, L ; Collins, FS ; Connell, JM ; Cooper, C ; Davey Smith, G ; Dennison, EM ; Deodhar, P ; Elliott, P ; Erdos, MR ; Estrada, K ; Evans, DM ; Gianniny, L ; Gieger, C ; Gillson, CJ ; Guiducci, C ; Hackett, R ; Hadley, D ; Hall, AS ; Havulinna, AS ; Hebebrand, J ; Hofman, A ; Isomaa, B ; Jacobs, KB ; Johnson, T ; Jousilahti, P ; Jovanovic, Z ; Khaw, KT ; Kraft, P ; Kuokkanen, M ; Kuusisto, J ; Laitinen, J ; Lakatta, EG ; Luan, J ; Luben, RN ; Mangino, M ; McArdle, WL ; Meitinger, T ; Mulas, A ; Munroe, PB ; Narisu, N ; Ness, A ; Northstone, K ; O'Rahilly, S ; Purmann, C ; Rees, MG ; Ridderstråle, M ; Ring, SM ; Rivadeneira, F ; Ruokonen, A ; Sandhu, MS ; Saramies, J ; Scott, LJ ; Scuteri, A ; Silander, K ; Sims, MA ; Song, K ; Stephens, J ; Stevens, S ; Stringham, HM ; Tung, YC ; Valle, TT ; Van Duijn, CM ; Vimaleswaran, KS ; Vollenweider, P ; Waeber, G ; Wallace, C ; Watanabe, RM ; Waterworth, DM ; Watkins, N ; Wellcome Trust Case Control, Consortium ; Witteman, JC ; Zeggini, E ; Zhai, G ; Zillikens, MC ; Altshuler, D ; Caulfield, MJ ; Chanock, SJ ; Farooqi, IS ; Ferrucci, L ; Guralnik, JM ; Hattersley, AT ; Hu, FB ; Jarvelin, MR ; Laakso, M ; Mooser, V ; Ong, KK ; Ouwehand, WH ; Salomaa, V ; Samani, NJ ; Spector, TD ; Tuomi, T ; Tuomilehto, J ; Uda, M ; Uitterlinden, AG ; Wareham, NJ ; Deloukas, P ; Frayling, TM ; Groop, LC ; Hayes, RB ; Hunter, DJ ; Mohlke, KL ; Peltonen, L ; Schlessinger, D ; Strachan, DP ; Wichmann, HE ; McCarthy, MI ; Boehnke, M ; Peltonen, L ; Schlessinger, D ; Strachan, DP ; Wichmann, HE ; McCarthy, MI ; Boehnke, M ; Barroso, I ; Abecasis, GR ; Hirschhorn, JN ; Genetic Investigation of ANthropometric Traits, Consortium. / Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. In: Nature Genetics. 2009 ; Vol. 41, No. 1. pp. 25-34.

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title = "Six new loci associated with body mass index highlight a neuronal influence on body weight regulation",

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.",

author = "CJ Willer and EK Speliotes and RJ Loos and S Li and CM Lindgren and IM Heid and SI Berndt and Al Elliott and AU Jackson and C Lamina and G Lettre and N Lim and HN Lyon and SA McCarroll and K Papadakis and L Qi and JC Randall and Rm Roccasecca and S Sanna and P Scheet and MN Weedon and E Wheeler and JH Zhao and LC Jacobs and I Prokopenko and N Soranzo and T Tanaka and Timpson, {Nicholas John} and P Almgren and A Bennett and RN Bergman and SA Bingham and LL Bonnycastle and M Brown and NP Burtt and P Chines and L Coin and FS Collins and JM Connell and C Cooper and {Davey Smith}, G and EM Dennison and P Deodhar and P Elliott and MR Erdos and K Estrada and DM Evans and L Gianniny and C Gieger and CJ Gillson and C Guiducci and R Hackett and D Hadley and AS Hall and AS Havulinna and J Hebebrand and A Hofman and B Isomaa and KB Jacobs and T Johnson and P Jousilahti and Z Jovanovic and KT Khaw and P Kraft and M Kuokkanen and J Kuusisto and J Laitinen and EG Lakatta and J Luan and RN Luben and M Mangino and WL McArdle and T Meitinger and A Mulas and PB Munroe and N Narisu and A Ness and K Northstone and S O'Rahilly and C Purmann and MG Rees and M Ridderstr{\aa}le and SM Ring and F Rivadeneira and A Ruokonen and MS Sandhu and J Saramies and LJ Scott and A Scuteri and K Silander and MA Sims and K Song and J Stephens and S Stevens and HM Stringham and YC Tung and TT Valle and {Van Duijn}, CM and KS Vimaleswaran and P Vollenweider and G Waeber and C Wallace and RM Watanabe and DM Waterworth and N Watkins and {Wellcome Trust Case Control}, Consortium and JC Witteman and E Zeggini and G Zhai and MC Zillikens and D Altshuler and MJ Caulfield and SJ Chanock and IS Farooqi and L Ferrucci and JM Guralnik and AT Hattersley and FB Hu and MR Jarvelin and M Laakso and V Mooser and KK Ong and WH Ouwehand and V Salomaa and NJ Samani and TD Spector and T Tuomi and J Tuomilehto and M Uda and AG Uitterlinden and NJ Wareham and P Deloukas and TM Frayling and LC Groop and RB Hayes and DJ Hunter and KL Mohlke and L Peltonen and D Schlessinger and DP Strachan and HE Wichmann and MI McCarthy and M Boehnke and L Peltonen and D Schlessinger and DP Strachan and HE Wichmann and MI McCarthy and M Boehnke and I Barroso and GR Abecasis and JN Hirschhorn and {Genetic Investigation of ANthropometric Traits}, Consortium",

note = "Publisher: Nature Pub. Co",

year = "2009",

doi = "10.1038/ng.287",

language = "English",

volume = "41",

pages = "25--34",

journal = "Nature Genetics",

issn = "1061-4036",

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Willer, CJ, Speliotes, EK, Loos, RJ, Li, S, Lindgren, CM, Heid, IM, Berndt, SI, Elliott, A, Jackson, AU, Lamina, C, Lettre, G, Lim, N, Lyon, HN, McCarroll, SA, Papadakis, K, Qi, L, Randall, JC, Roccasecca, R, Sanna, S, Scheet, P, Weedon, MN, Wheeler, E, Zhao, JH, Jacobs, LC, Prokopenko, I, Soranzo, N, Tanaka, T, Timpson, NJ, Almgren, P, Bennett, A, Bergman, RN, Bingham, SA, Bonnycastle, LL, Brown, M, Burtt, NP, Chines, P, Coin, L, Collins, FS, Connell, JM, Cooper, C, Davey Smith, G, Dennison, EM, Deodhar, P, Elliott, P, Erdos, MR, Estrada, K, Evans, DM, Gianniny, L, Gieger, C, Gillson, CJ, Guiducci, C, Hackett, R, Hadley, D, Hall, AS, Havulinna, AS, Hebebrand, J, Hofman, A, Isomaa, B, Jacobs, KB, Johnson, T, Jousilahti, P, Jovanovic, Z, Khaw, KT, Kraft, P, Kuokkanen, M, Kuusisto, J, Laitinen, J, Lakatta, EG, Luan, J, Luben, RN, Mangino, M, McArdle, WL, Meitinger, T, Mulas, A, Munroe, PB, Narisu, N, Ness, A, Northstone, K, O'Rahilly, S, Purmann, C, Rees, MG, Ridderstråle, M, Ring, SM, Rivadeneira, F, Ruokonen, A, Sandhu, MS, Saramies, J, Scott, LJ, Scuteri, A, Silander, K, Sims, MA, Song, K, Stephens, J, Stevens, S, Stringham, HM, Tung, YC, Valle, TT, Van Duijn, CM, Vimaleswaran, KS, Vollenweider, P, Waeber, G, Wallace, C, Watanabe, RM, Waterworth, DM, Watkins, N, Wellcome Trust Case Control, C, Witteman, JC, Zeggini, E, Zhai, G, Zillikens, MC, Altshuler, D, Caulfield, MJ, Chanock, SJ, Farooqi, IS, Ferrucci, L, Guralnik, JM, Hattersley, AT, Hu, FB, Jarvelin, MR, Laakso, M, Mooser, V, Ong, KK, Ouwehand, WH, Salomaa, V, Samani, NJ, Spector, TD, Tuomi, T, Tuomilehto, J, Uda, M, Uitterlinden, AG, Wareham, NJ, Deloukas, P, Frayling, TM, Groop, LC, Hayes, RB, Hunter, DJ, Mohlke, KL, Peltonen, L, Schlessinger, D, Strachan, DP, Wichmann, HE, McCarthy, MI, Boehnke, M, Peltonen, L, Schlessinger, D, Strachan, DP, Wichmann, HE, McCarthy, MI, Boehnke, M, Barroso, I, Abecasis, GR, Hirschhorn, JN & Genetic Investigation of ANthropometric Traits, C 2009, 'Six new loci associated with body mass index highlight a neuronal influence on body weight regulation', Nature Genetics, vol. 41, no. 1, pp. 25-34. https://doi.org/10.1038/ng.287

Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. / Willer, CJ; Speliotes, EK; Loos, RJ; Li, S; Lindgren, CM; Heid, IM; Berndt, SI; Elliott, Al; Jackson, AU; Lamina, C; Lettre, G; Lim, N; Lyon, HN; McCarroll, SA; Papadakis, K; Qi, L; Randall, JC; Roccasecca, Rm; Sanna, S; Scheet, P; Weedon, MN; Wheeler, E; Zhao, JH; Jacobs, LC; Prokopenko, I; Soranzo, N; Tanaka, T; Timpson, Nicholas John; Almgren, P; Bennett, A; Bergman, RN; Bingham, SA; Bonnycastle, LL; Brown, M; Burtt, NP; Chines, P; Coin, L; Collins, FS; Connell, JM; Cooper, C; Davey Smith, G; Dennison, EM; Deodhar, P; Elliott, P; Erdos, MR; Estrada, K; Evans, DM; Gianniny, L; Gieger, C; Gillson, CJ; Guiducci, C; Hackett, R; Hadley, D; Hall, AS; Havulinna, AS; Hebebrand, J; Hofman, A; Isomaa, B; Jacobs, KB; Johnson, T; Jousilahti, P; Jovanovic, Z; Khaw, KT; Kraft, P; Kuokkanen, M; Kuusisto, J; Laitinen, J; Lakatta, EG; Luan, J; Luben, RN; Mangino, M; McArdle, WL; Meitinger, T; Mulas, A; Munroe, PB; Narisu, N; Ness, A; Northstone, K; O'Rahilly, S; Purmann, C; Rees, MG; Ridderstråle, M; Ring, SM; Rivadeneira, F; Ruokonen, A; Sandhu, MS; Saramies, J; Scott, LJ; Scuteri, A; Silander, K; Sims, MA; Song, K; Stephens, J; Stevens, S; Stringham, HM; Tung, YC; Valle, TT; Van Duijn, CM; Vimaleswaran, KS; Vollenweider, P; Waeber, G; Wallace, C; Watanabe, RM; Waterworth, DM; Watkins, N; Wellcome Trust Case Control, Consortium; Witteman, JC; Zeggini, E; Zhai, G; Zillikens, MC; Altshuler, D; Caulfield, MJ; Chanock, SJ; Farooqi, IS; Ferrucci, L; Guralnik, JM; Hattersley, AT; Hu, FB; Jarvelin, MR; Laakso, M; Mooser, V; Ong, KK; Ouwehand, WH; Salomaa, V; Samani, NJ; Spector, TD; Tuomi, T; Tuomilehto, J; Uda, M; Uitterlinden, AG; Wareham, NJ; Deloukas, P; Frayling, TM; Groop, LC; Hayes, RB; Hunter, DJ; Mohlke, KL; Peltonen, L; Schlessinger, D; Strachan, DP; Wichmann, HE; McCarthy, MI; Boehnke, M; Peltonen, L; Schlessinger, D; Strachan, DP; Wichmann, HE; McCarthy, MI; Boehnke, M; Barroso, I; Abecasis, GR; Hirschhorn, JN; Genetic Investigation of ANthropometric Traits, Consortium.

In: Nature Genetics, Vol. 41, No. 1, 2009, p. 25-34.

Research output: Contribution to journal › Article (Academic Journal) › peer-review

TY - JOUR

T1 - Six new loci associated with body mass index highlight a neuronal influence on body weight regulation

AU - Willer, CJ

AU - Speliotes, EK

AU - Loos, RJ

AU - Li, S

AU - Lindgren, CM

AU - Heid, IM

AU - Berndt, SI

AU - Elliott, Al

AU - Jackson, AU

AU - Lamina, C

AU - Lettre, G

AU - Lim, N

AU - Lyon, HN

AU - McCarroll, SA

AU - Papadakis, K

AU - Qi, L

AU - Randall, JC

AU - Roccasecca, Rm

AU - Sanna, S

AU - Scheet, P

AU - Weedon, MN

AU - Wheeler, E

AU - Zhao, JH

AU - Jacobs, LC

AU - Prokopenko, I

AU - Soranzo, N

AU - Tanaka, T

AU - Timpson, Nicholas John

AU - Almgren, P

AU - Bennett, A

AU - Bergman, RN

AU - Bingham, SA

AU - Bonnycastle, LL

AU - Brown, M

AU - Burtt, NP

AU - Chines, P

AU - Coin, L

AU - Collins, FS

AU - Connell, JM

AU - Cooper, C

AU - Davey Smith, G

AU - Dennison, EM

AU - Deodhar, P

AU - Elliott, P

AU - Erdos, MR

AU - Estrada, K

AU - Evans, DM

AU - Gianniny, L

AU - Gieger, C

AU - Gillson, CJ

AU - Guiducci, C

AU - Hackett, R

AU - Hadley, D

AU - Hall, AS

AU - Havulinna, AS

AU - Hebebrand, J

AU - Hofman, A

AU - Isomaa, B

AU - Jacobs, KB

AU - Johnson, T

AU - Jousilahti, P

AU - Jovanovic, Z

AU - Khaw, KT

AU - Kraft, P

AU - Kuokkanen, M

AU - Kuusisto, J

AU - Laitinen, J

AU - Lakatta, EG

AU - Luan, J

AU - Luben, RN

AU - Mangino, M

AU - McArdle, WL

AU - Meitinger, T

AU - Mulas, A

AU - Munroe, PB

AU - Narisu, N

AU - Ness, A

AU - Northstone, K

AU - O'Rahilly, S

AU - Purmann, C

AU - Rees, MG

AU - Ridderstråle, M

AU - Ring, SM

AU - Rivadeneira, F

AU - Ruokonen, A

AU - Sandhu, MS

AU - Saramies, J

AU - Scott, LJ

AU - Scuteri, A

AU - Silander, K

AU - Sims, MA

AU - Song, K

AU - Stephens, J

AU - Stevens, S

AU - Stringham, HM

AU - Tung, YC

AU - Valle, TT

AU - Van Duijn, CM

AU - Vimaleswaran, KS

AU - Vollenweider, P

AU - Waeber, G

AU - Wallace, C

AU - Watanabe, RM

AU - Waterworth, DM

AU - Watkins, N

AU - Wellcome Trust Case Control, Consortium

AU - Witteman, JC

AU - Zeggini, E

AU - Zhai, G

AU - Zillikens, MC

AU - Altshuler, D

AU - Caulfield, MJ

AU - Chanock, SJ

AU - Farooqi, IS

AU - Ferrucci, L

AU - Guralnik, JM

AU - Hattersley, AT

AU - Hu, FB

AU - Jarvelin, MR

AU - Laakso, M

AU - Mooser, V

AU - Ong, KK

AU - Ouwehand, WH

AU - Salomaa, V

AU - Samani, NJ

AU - Spector, TD

AU - Tuomi, T

AU - Tuomilehto, J

AU - Uda, M

AU - Uitterlinden, AG

AU - Wareham, NJ

AU - Deloukas, P

AU - Frayling, TM

AU - Groop, LC

AU - Hayes, RB

AU - Hunter, DJ

AU - Mohlke, KL

AU - Peltonen, L

AU - Schlessinger, D

AU - Strachan, DP

AU - Wichmann, HE

AU - McCarthy, MI

AU - Boehnke, M

AU - Peltonen, L

AU - Schlessinger, D

AU - Strachan, DP

AU - Wichmann, HE

AU - McCarthy, MI

AU - Boehnke, M

AU - Barroso, I

AU - Abecasis, GR

AU - Hirschhorn, JN

AU - Genetic Investigation of ANthropometric Traits, Consortium

N1 - Publisher: Nature Pub. Co

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

U2 - 10.1038/ng.287

DO - 10.1038/ng.287

M3 - Article (Academic Journal)

C2 - 19079261

VL - 41

SP - 25

EP - 34

JO - Nature Genetics

JF - Nature Genetics

SN - 1061-4036

IS - 1

ER -

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

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