Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution

IM Heid; AU Jackson; JC Randall; TW Winkler; L Qi; V Steinthorsdottir; G Thorleifsson; M.C. Zillikens; EK Speliotes; R Magi; T Workalemahu; CC White; N Bouatia-Naji; TB Harris; SI Berndt; E Ingelsson; CJ Willer; MN Weedon; JA Luan; S Vedantam; T Esko; TO Kilpelainen; Z Kutalik; SX Li; KL Monda; AL Dixon; CC Holmes; LM Kaplan; LM Liang; JL Min; MF Moffatt; C Molony; G Nicholson; EE Schadt; KT Zondervan; MF Feitosa; T Ferreira; HL Allen; RJ Weyant; E Wheeler; AR Wood; Karol Estrada Gil; ME Goddard; G Lettre; M Mangino; DR Nyholt; S Purcell; AV Smith; PM Visscher; JA Yang; SA McCarroll; J Nemesh; BF Voight; D Absher; Najaf Amin; T Aspelund; L Coin; NL Glazer; C Hayward; NL Heard-Costa; JJ (Jouke Jan) Hottenga; A Johansson; T Johnson; M Kaakinen; K Kapur; S Ketkar; JW Knowles; P Kraft; AT Kraja; C Lamina; MF Leitzmann; B McKnight; AP Morris; KK Ong; JRB Perry; Marjolein Peters; O Polasek; I Prokopenko; NW Rayner; S Ripatti; Fernando Rivadeneira; NR Robertson; S Sanna; U Sovio; I Surakka; A Teumer; S van Wingerden; V Vitart; JH Zhao; C Cavalcanti-Proenca; PS Chines; E Fisher; JR Kulzer; C Lecoeur; N Narisu; C Sandholt; LJ Scott; K Silander; K Stark; ML Tammesoo; TM Teslovich; NJ Timpson; RM Watanabe; R Welch; DI Chasman; MN Cooper; JO Jansson; J Kettunen; RW Lawrence; N Pellikka; M Perola; L Vandenput; H Alavere; P Almgren; LD Atwood; AJ Bennett; R Biffar; LL Bonnycastle; SR Bornstein; TA Buchanan; H Campbell; INM Day; M Dei; M Dorr; P Elliott; MR Erdos; JG Eriksson; NB Freimer; M Fu; S Gaget; EJC de Geus; AP Gjesing; H Grallert; J Grassler; CJ Groves; C Guiducci; AL Hartikainen; N Hassanali; AS Havulinna; KH Herzig; AA Hicks; JN Hui; W Igl; P Jousilahti; A Jula; E Kajantie; L Kinnunen; I Kolcic; S Koskinen; P Kovacs; HK Kroemer; V Krzelj; J Kuusisto; K Kvaloy; J Laitinen; O Lantieri; GM Lathrop; ML Lokki; RN Luben; B Ludwig; WL McArdle; A McCarthy; MA Morken; M Nelis; MJ Neville; G Pare; AN Parker; JF Peden; I Pichler; KH Pietilainen; CGP Platou; A Pouta; M Ridderstrale; NJ Samani; J Saramies; J Sinisalo; JH Smit; RJ Strawbridge; HM Stringham; AJ Swift; M Teder-Laving; B Thomson; G Usala; Joyce van Meurs; GJ van Ommen; V Vatin; CB Volpato; H Wallaschofski; GB Walters; E Widen; SH Wild; G Willemsen; DR Witte; L Zgaga; P Zitting; JP Beilby; AL James; M Kahonen; T Lehtimaki; MS Nieminen; C Ohlsson; LJ Palmer; O Raitakari; PM Ridker; M Stumvoll; A Tonjes; J Viikari; B Balkau; Y Ben-Shlomo; RN Bergman; H Boeing; GD Smith; S Ebrahim; P Froguel; T Hansen; C Hengstenberg; K Hveem; B Isomaa; T Jorgensen; F Karpe; KT Khaw; M Laakso; DA Lawlor; M (Michel) Marre; T Meitinger; A Metspalu; K Midthjell; O Pedersen; V Salomaa; PEH Schwarz; T Tuomi; J Tuomilehto; TT Valle; NJ Wareham; AM Arnold; JS Beckmann; S Bergmann; E Boerwinkle; DI Boomsma; MJ Caulfield; FS Collins; G Eiriksdottir; V Gudnason; U Gyllensten; A Hamsten; AT Hattersley; Bert Hofman; FB Hu; T Illig; C Iribarren; MR Jarvelin; WHL Kao; J Kaprio; LJ (Lenore) Launer; PB Munroe; Ben Oostra; BW Penninx; PP Pramstaller; BM Psaty; T Quertermous; A Rissanen; I Rudan; AR Shuldiner; N Soranzo; TD Spector; AC Syvanen; M Uda; André Uitterlinden; H Volzke; P Vollenweider; JF Wilson; JCM Witteman; AF Wright; GR Abecasis; M Boehnke; IB Borecki; P Deloukas; TM Frayling; LC Groop; T Haritunians; DJ Hunter; RC Kaplan; KE North; JR O'Connell; L Peltonen; D Schlessinger; DP Strachan; JN Hirschhorn; TL Assimes; HE Wichmann; U Thorsteinsdottir; Cornelia Duijn; K Stefansson; LA Cupples; RJF Loos; I Barroso; MI McCarthy; CS Fox; KL Mohlke; CM Lindgren

doi:10.1038/ng.685

Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution

IM Heid, AU Jackson, JC Randall, TW Winkler, L Qi, V Steinthorsdottir, G Thorleifsson, M.C. Zillikens, EK Speliotes, R Magi, T Workalemahu, CC White, N Bouatia-Naji, TB Harris, SI Berndt, E Ingelsson, CJ Willer, MN Weedon, JA Luan, S VedantamT Esko, TO Kilpelainen, Z Kutalik, SX Li, KL Monda, AL Dixon, CC Holmes, LM Kaplan, LM Liang, JL Min, MF Moffatt, C Molony, G Nicholson, EE Schadt, KT Zondervan, MF Feitosa, T Ferreira, HL Allen, RJ Weyant, E Wheeler, AR Wood, Karol Estrada Gil, ME Goddard, G Lettre, M Mangino, DR Nyholt, S Purcell, AV Smith, PM Visscher, JA Yang, SA McCarroll, J Nemesh, BF Voight, D Absher, Najaf Amin, T Aspelund, L Coin, NL Glazer, C Hayward, NL Heard-Costa, JJ (Jouke Jan) Hottenga, A Johansson, T Johnson, M Kaakinen, K Kapur, S Ketkar, JW Knowles, P Kraft, AT Kraja, C Lamina, MF Leitzmann, B McKnight, AP Morris, KK Ong, JRB Perry, Marjolein Peters, O Polasek, I Prokopenko, NW Rayner, S Ripatti, Fernando Rivadeneira, NR Robertson, S Sanna, U Sovio, I Surakka, A Teumer, S van Wingerden, V Vitart, JH Zhao, C Cavalcanti-Proenca, PS Chines, E Fisher, JR Kulzer, C Lecoeur, N Narisu, C Sandholt, LJ Scott, K Silander, K Stark, ML Tammesoo, TM Teslovich, NJ Timpson, RM Watanabe, R Welch, DI Chasman, MN Cooper, JO Jansson, J Kettunen, RW Lawrence, N Pellikka, M Perola, L Vandenput, H Alavere, P Almgren, LD Atwood, AJ Bennett, R Biffar, LL Bonnycastle, SR Bornstein, TA Buchanan, H Campbell, INM Day, M Dei, M Dorr, P Elliott, MR Erdos, JG Eriksson, NB Freimer, M Fu, S Gaget, EJC de Geus, AP Gjesing, H Grallert, J Grassler, CJ Groves, C Guiducci, AL Hartikainen, N Hassanali, AS Havulinna, KH Herzig, AA Hicks, JN Hui, W Igl, P Jousilahti, A Jula, E Kajantie, L Kinnunen, I Kolcic, S Koskinen, P Kovacs, HK Kroemer, V Krzelj, J Kuusisto, K Kvaloy, J Laitinen, O Lantieri, GM Lathrop, ML Lokki, RN Luben, B Ludwig, WL McArdle, A McCarthy, MA Morken, M Nelis, MJ Neville, G Pare, AN Parker, JF Peden, I Pichler, KH Pietilainen, CGP Platou, A Pouta, M Ridderstrale, NJ Samani, J Saramies, J Sinisalo, JH Smit, RJ Strawbridge, HM Stringham, AJ Swift, M Teder-Laving, B Thomson, G Usala, Joyce van Meurs, GJ van Ommen, V Vatin, CB Volpato, H Wallaschofski, GB Walters, E Widen, SH Wild, G Willemsen, DR Witte, L Zgaga, P Zitting, JP Beilby, AL James, M Kahonen, T Lehtimaki, MS Nieminen, C Ohlsson, LJ Palmer, O Raitakari, PM Ridker, M Stumvoll, A Tonjes, J Viikari, B Balkau, Y Ben-Shlomo, RN Bergman, H Boeing, GD Smith, S Ebrahim, P Froguel, T Hansen, C Hengstenberg, K Hveem, B Isomaa, T Jorgensen, F Karpe, KT Khaw, M Laakso, DA Lawlor, M (Michel) Marre, T Meitinger, A Metspalu, K Midthjell, O Pedersen, V Salomaa, PEH Schwarz, T Tuomi, J Tuomilehto, TT Valle, NJ Wareham, AM Arnold, JS Beckmann, S Bergmann, E Boerwinkle, DI Boomsma, MJ Caulfield, FS Collins, G Eiriksdottir, V Gudnason, U Gyllensten, A Hamsten, AT Hattersley, Bert Hofman, FB Hu, T Illig, C Iribarren, MR Jarvelin, WHL Kao, J Kaprio, LJ (Lenore) Launer, PB Munroe, Ben Oostra, BW Penninx, PP Pramstaller, BM Psaty, T Quertermous, A Rissanen, I Rudan, AR Shuldiner, N Soranzo, TD Spector, AC Syvanen, M Uda, André Uitterlinden, H Volzke, P Vollenweider, JF Wilson, JCM Witteman, AF Wright, GR Abecasis, M Boehnke, IB Borecki, P Deloukas, TM Frayling, LC Groop, T Haritunians, DJ Hunter, RC Kaplan, KE North, JR O'Connell, L Peltonen, D Schlessinger, DP Strachan, JN Hirschhorn, TL Assimes, HE Wichmann, U Thorsteinsdottir, Cornelia Duijn, K Stefansson, LA Cupples, RJF Loos, I Barroso, MI McCarthy, CS Fox, KL Mohlke, CM Lindgren

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

791 Citations (Scopus)

Abstract

Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 x 10(-9) to P = 1.8 x 10(-40)) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 x 10(-3) to P = 1.2 x 10(-13)). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.

Original language	Undefined/Unknown
Pages (from-to)	949-U160
Journal	Nature Genetics
Volume	42
Issue number	11
DOIs	https://doi.org/10.1038/ng.685
Publication status	Published - 2010

Research programs

EMC MGC-02-96-01
EMC MM-01-39-02
EMC NIHES-01-64-02

Access to Document

10.1038/ng.685

http://hdl.handle.net/1765/28358

Cite this

Heid, IM., Jackson, AU., Randall, JC., Winkler, TW., Qi, L., Steinthorsdottir, V., Thorleifsson, G., Zillikens, M. C., Speliotes, EK., Magi, R., Workalemahu, T., White, CC., Bouatia-Naji, N., Harris, TB., Berndt, SI., Ingelsson, E., Willer, CJ., Weedon, MN., Luan, JA., ... Lindgren, CM. (2010). Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution. Nature Genetics, 42(11), 949-U160. https://doi.org/10.1038/ng.685

@article{69d7ec5257ed4acfa7cda0e60f1d6804,

title = "Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution",

abstract = "Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 x 10(-9) to P = 1.8 x 10(-40)) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 x 10(-3) to P = 1.2 x 10(-13)). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.",

author = "IM Heid and AU Jackson and JC Randall and TW Winkler and L Qi and V Steinthorsdottir and G Thorleifsson and M.C. Zillikens and EK Speliotes and R Magi and T Workalemahu and CC White and N Bouatia-Naji and TB Harris and SI Berndt and E Ingelsson and CJ Willer and MN Weedon and JA Luan and S Vedantam and T Esko and TO Kilpelainen and Z Kutalik and SX Li and KL Monda and AL Dixon and CC Holmes and LM Kaplan and LM Liang and JL Min and MF Moffatt and C Molony and G Nicholson and EE Schadt and KT Zondervan and MF Feitosa and T Ferreira and HL Allen and RJ Weyant and E Wheeler and AR Wood and {Estrada Gil}, Karol and ME Goddard and G Lettre and M Mangino and DR Nyholt and S Purcell and AV Smith and PM Visscher and JA Yang and SA McCarroll and J Nemesh and BF Voight and D Absher and Najaf Amin and T Aspelund and L Coin and NL Glazer and C Hayward and NL Heard-Costa and Hottenga, {JJ (Jouke Jan)} and A Johansson and T Johnson and M Kaakinen and K Kapur and S Ketkar and JW Knowles and P Kraft and AT Kraja and C Lamina and MF Leitzmann and B McKnight and AP Morris and KK Ong and JRB Perry and Marjolein Peters and O Polasek and I Prokopenko and NW Rayner and S Ripatti and Fernando Rivadeneira and NR Robertson and S Sanna and U Sovio and I Surakka and A Teumer and {van Wingerden}, S and V Vitart and JH Zhao and C Cavalcanti-Proenca and PS Chines and E Fisher and JR Kulzer and C Lecoeur and N Narisu and C Sandholt and LJ Scott and K Silander and K Stark and ML Tammesoo and TM Teslovich and NJ Timpson and RM Watanabe and R Welch and DI Chasman and MN Cooper and JO Jansson and J Kettunen and RW Lawrence and N Pellikka and M Perola and L Vandenput and H Alavere and P Almgren and LD Atwood and AJ Bennett and R Biffar and LL Bonnycastle and SR Bornstein and TA Buchanan and H Campbell and INM Day and M Dei and M Dorr and P Elliott and MR Erdos and JG Eriksson and NB Freimer and M Fu and S Gaget and {de Geus}, EJC and AP Gjesing and H Grallert and J Grassler and CJ Groves and C Guiducci and AL Hartikainen and N Hassanali and AS Havulinna and KH Herzig and AA Hicks and JN Hui and W Igl and P Jousilahti and A Jula and E Kajantie and L Kinnunen and I Kolcic and S Koskinen and P Kovacs and HK Kroemer and V Krzelj and J Kuusisto and K Kvaloy and J Laitinen and O Lantieri and GM Lathrop and ML Lokki and RN Luben and B Ludwig and WL McArdle and A McCarthy and MA Morken and M Nelis and MJ Neville and G Pare and AN Parker and JF Peden and I Pichler and KH Pietilainen and CGP Platou and A Pouta and M Ridderstrale and NJ Samani and J Saramies and J Sinisalo and JH Smit and RJ Strawbridge and HM Stringham and AJ Swift and M Teder-Laving and B Thomson and G Usala and {van Meurs}, Joyce and {van Ommen}, GJ and V Vatin and CB Volpato and H Wallaschofski and GB Walters and E Widen and SH Wild and G Willemsen and DR Witte and L Zgaga and P Zitting and JP Beilby and AL James and M Kahonen and T Lehtimaki and MS Nieminen and C Ohlsson and LJ Palmer and O Raitakari and PM Ridker and M Stumvoll and A Tonjes and J Viikari and B Balkau and Y Ben-Shlomo and RN Bergman and H Boeing and GD Smith and S Ebrahim and P Froguel and T Hansen and C Hengstenberg and K Hveem and B Isomaa and T Jorgensen and F Karpe and KT Khaw and M Laakso and DA Lawlor and Marre, {M (Michel)} and T Meitinger and A Metspalu and K Midthjell and O Pedersen and V Salomaa and PEH Schwarz and T Tuomi and J Tuomilehto and TT Valle and NJ Wareham and AM Arnold and JS Beckmann and S Bergmann and E Boerwinkle and DI Boomsma and MJ Caulfield and FS Collins and G Eiriksdottir and V Gudnason and U Gyllensten and A Hamsten and AT Hattersley and Bert Hofman and FB Hu and T Illig and C Iribarren and MR Jarvelin and WHL Kao and J Kaprio and Launer, {LJ (Lenore)} and PB Munroe and Ben Oostra and BW Penninx and PP Pramstaller and BM Psaty and T Quertermous and A Rissanen and I Rudan and AR Shuldiner and N Soranzo and TD Spector and AC Syvanen and M Uda and Andr{\'e} Uitterlinden and H Volzke and P Vollenweider and JF Wilson and JCM Witteman and AF Wright and GR Abecasis and M Boehnke and IB Borecki and P Deloukas and TM Frayling and LC Groop and T Haritunians and DJ Hunter and RC Kaplan and KE North and JR O'Connell and L Peltonen and D Schlessinger and DP Strachan and JN Hirschhorn and TL Assimes and HE Wichmann and U Thorsteinsdottir and Cornelia Duijn and K Stefansson and LA Cupples and RJF Loos and I Barroso and MI McCarthy and CS Fox and KL Mohlke and CM Lindgren",

year = "2010",

doi = "10.1038/ng.685",

language = "Undefined/Unknown",

volume = "42",

pages = "949--U160",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "11",

}

Heid, IM, Jackson, AU, Randall, JC, Winkler, TW, Qi, L, Steinthorsdottir, V, Thorleifsson, G, Zillikens, MC, Speliotes, EK, Magi, R, Workalemahu, T, White, CC, Bouatia-Naji, N, Harris, TB, Berndt, SI, Ingelsson, E, Willer, CJ, Weedon, MN, Luan, JA, Vedantam, S, Esko, T, Kilpelainen, TO, Kutalik, Z, Li, SX, Monda, KL, Dixon, AL, Holmes, CC, Kaplan, LM, Liang, LM, Min, JL, Moffatt, MF, Molony, C, Nicholson, G, Schadt, EE, Zondervan, KT, Feitosa, MF, Ferreira, T, Allen, HL, Weyant, RJ, Wheeler, E, Wood, AR, Estrada Gil, K, Goddard, ME, Lettre, G, Mangino, M, Nyholt, DR, Purcell, S, Smith, AV, Visscher, PM, Yang, JA, McCarroll, SA, Nemesh, J, Voight, BF, Absher, D, Amin, N, Aspelund, T, Coin, L, Glazer, NL, Hayward, C, Heard-Costa, NL, Hottenga, JJ, Johansson, A, Johnson, T, Kaakinen, M, Kapur, K, Ketkar, S, Knowles, JW, Kraft, P, Kraja, AT, Lamina, C, Leitzmann, MF, McKnight, B, Morris, AP, Ong, KK, Perry, JRB, Peters, M, Polasek, O, Prokopenko, I, Rayner, NW, Ripatti, S, Rivadeneira, F, Robertson, NR, Sanna, S, Sovio, U, Surakka, I, Teumer, A, van Wingerden, S, Vitart, V, Zhao, JH, Cavalcanti-Proenca, C, Chines, PS, Fisher, E, Kulzer, JR, Lecoeur, C, Narisu, N, Sandholt, C, Scott, LJ, Silander, K, Stark, K, Tammesoo, ML, Teslovich, TM, Timpson, NJ, Watanabe, RM, Welch, R, Chasman, DI, Cooper, MN, Jansson, JO, Kettunen, J, Lawrence, RW, Pellikka, N, Perola, M, Vandenput, L, Alavere, H, Almgren, P, Atwood, LD, Bennett, AJ, Biffar, R, Bonnycastle, LL, Bornstein, SR, Buchanan, TA, Campbell, H, Day, INM, Dei, M, Dorr, M, Elliott, P, Erdos, MR, Eriksson, JG, Freimer, NB, Fu, M, Gaget, S, de Geus, EJC, Gjesing, AP, Grallert, H, Grassler, J, Groves, CJ, Guiducci, C, Hartikainen, AL, Hassanali, N, Havulinna, AS, Herzig, KH, Hicks, AA, Hui, JN, Igl, W, Jousilahti, P, Jula, A, Kajantie, E, Kinnunen, L, Kolcic, I, Koskinen, S, Kovacs, P, Kroemer, HK, Krzelj, V, Kuusisto, J, Kvaloy, K, Laitinen, J, Lantieri, O, Lathrop, GM, Lokki, ML, Luben, RN, Ludwig, B, McArdle, WL, McCarthy, A, Morken, MA, Nelis, M, Neville, MJ, Pare, G, Parker, AN, Peden, JF, Pichler, I, Pietilainen, KH, Platou, CGP, Pouta, A, Ridderstrale, M, Samani, NJ, Saramies, J, Sinisalo, J, Smit, JH, Strawbridge, RJ, Stringham, HM, Swift, AJ, Teder-Laving, M, Thomson, B, Usala, G, van Meurs, J, van Ommen, GJ, Vatin, V, Volpato, CB, Wallaschofski, H, Walters, GB, Widen, E, Wild, SH, Willemsen, G, Witte, DR, Zgaga, L, Zitting, P, Beilby, JP, James, AL, Kahonen, M, Lehtimaki, T, Nieminen, MS, Ohlsson, C, Palmer, LJ, Raitakari, O, Ridker, PM, Stumvoll, M, Tonjes, A, Viikari, J, Balkau, B, Ben-Shlomo, Y, Bergman, RN, Boeing, H, Smith, GD, Ebrahim, S, Froguel, P, Hansen, T, Hengstenberg, C, Hveem, K, Isomaa, B, Jorgensen, T, Karpe, F, Khaw, KT, Laakso, M, Lawlor, DA, Marre, M, Meitinger, T, Metspalu, A, Midthjell, K, Pedersen, O, Salomaa, V, Schwarz, PEH, Tuomi, T, Tuomilehto, J, Valle, TT, Wareham, NJ, Arnold, AM, Beckmann, JS, Bergmann, S, Boerwinkle, E, Boomsma, DI, Caulfield, MJ, Collins, FS, Eiriksdottir, G, Gudnason, V, Gyllensten, U, Hamsten, A, Hattersley, AT, Hofman, B, Hu, FB, Illig, T, Iribarren, C, Jarvelin, MR, Kao, WHL, Kaprio, J, Launer, LJ, Munroe, PB, Oostra, B, Penninx, BW, Pramstaller, PP, Psaty, BM, Quertermous, T, Rissanen, A, Rudan, I, Shuldiner, AR, Soranzo, N, Spector, TD, Syvanen, AC, Uda, M, Uitterlinden, A, Volzke, H, Vollenweider, P, Wilson, JF, Witteman, JCM, Wright, AF, Abecasis, GR, Boehnke, M, Borecki, IB, Deloukas, P, Frayling, TM, Groop, LC, Haritunians, T, Hunter, DJ, Kaplan, RC, North, KE, O'Connell, JR, Peltonen, L, Schlessinger, D, Strachan, DP, Hirschhorn, JN, Assimes, TL, Wichmann, HE, Thorsteinsdottir, U, Duijn, C, Stefansson, K, Cupples, LA, Loos, RJF, Barroso, I, McCarthy, MI, Fox, CS, Mohlke, KL & Lindgren, CM 2010, 'Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution', Nature Genetics, vol. 42, no. 11, pp. 949-U160. https://doi.org/10.1038/ng.685

TY - JOUR

T1 - Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution

AU - Heid, IM

AU - Jackson, AU

AU - Randall, JC

AU - Winkler, TW

AU - Qi, L

AU - Steinthorsdottir, V

AU - Thorleifsson, G

AU - Zillikens, M.C.

AU - Speliotes, EK

AU - Magi, R

AU - Workalemahu, T

AU - White, CC

AU - Bouatia-Naji, N

AU - Harris, TB

AU - Berndt, SI

AU - Ingelsson, E

AU - Willer, CJ

AU - Weedon, MN

AU - Luan, JA

AU - Vedantam, S

AU - Esko, T

AU - Kilpelainen, TO

AU - Kutalik, Z

AU - Li, SX

AU - Monda, KL

AU - Dixon, AL

AU - Holmes, CC

AU - Kaplan, LM

AU - Liang, LM

AU - Min, JL

AU - Moffatt, MF

AU - Molony, C

AU - Nicholson, G

AU - Schadt, EE

AU - Zondervan, KT

AU - Feitosa, MF

AU - Ferreira, T

AU - Allen, HL

AU - Weyant, RJ

AU - Wheeler, E

AU - Wood, AR

AU - Estrada Gil, Karol

AU - Goddard, ME

AU - Lettre, G

AU - Mangino, M

AU - Nyholt, DR

AU - Purcell, S

AU - Smith, AV

AU - Visscher, PM

AU - Yang, JA

AU - McCarroll, SA

AU - Nemesh, J

AU - Voight, BF

AU - Absher, D

AU - Amin, Najaf

AU - Aspelund, T

AU - Coin, L

AU - Glazer, NL

AU - Hayward, C

AU - Heard-Costa, NL

AU - Hottenga, JJ (Jouke Jan)

AU - Johansson, A

AU - Johnson, T

AU - Kaakinen, M

AU - Kapur, K

AU - Ketkar, S

AU - Knowles, JW

AU - Kraft, P

AU - Kraja, AT

AU - Lamina, C

AU - Leitzmann, MF

AU - McKnight, B

AU - Morris, AP

AU - Ong, KK

AU - Perry, JRB

AU - Peters, Marjolein

AU - Polasek, O

AU - Prokopenko, I

AU - Rayner, NW

AU - Ripatti, S

AU - Rivadeneira, Fernando

AU - Robertson, NR

AU - Sanna, S

AU - Sovio, U

AU - Surakka, I

AU - Teumer, A

AU - van Wingerden, S

AU - Vitart, V

AU - Zhao, JH

AU - Cavalcanti-Proenca, C

AU - Chines, PS

AU - Fisher, E

AU - Kulzer, JR

AU - Lecoeur, C

AU - Narisu, N

AU - Sandholt, C

AU - Scott, LJ

AU - Silander, K

AU - Stark, K

AU - Tammesoo, ML

AU - Teslovich, TM

AU - Timpson, NJ

AU - Watanabe, RM

AU - Welch, R

AU - Chasman, DI

AU - Cooper, MN

AU - Jansson, JO

AU - Kettunen, J

AU - Lawrence, RW

AU - Pellikka, N

AU - Perola, M

AU - Vandenput, L

AU - Alavere, H

AU - Almgren, P

AU - Atwood, LD

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PY - 2010

Y1 - 2010

N2 - Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 x 10(-9) to P = 1.8 x 10(-40)) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 x 10(-3) to P = 1.2 x 10(-13)). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.

AB - Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 x 10(-9) to P = 1.8 x 10(-40)) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 x 10(-3) to P = 1.2 x 10(-13)). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.

U2 - 10.1038/ng.685

DO - 10.1038/ng.685

M3 - Article

C2 - 20935629

SN - 1061-4036

VL - 42

SP - 949-U160

JO - Nature Genetics

JF - Nature Genetics

IS - 11

ER -