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

I.M. Heid; A.U. Jackson; J.C. Randall; T.W. Winkler; L. Qi; V. Steinthorsdottir; G. Thorleifsson; M.C. Zillikens; E.K. Speliotes; R. Mägi; T. Workalemahu; C.C. White; N. Bouatia-Naji; T.B. Harris; S.I. Berndt; E. Ingelsson; C.J. Willer; M.N. Weedon; J. Luan; S. Vedantam; T. Esko; T.O. Kilpeläinen; Z. Kutalik; S. Li; K.L. Monda; A.L. Dixon; C.C. Holmes; L.M. Kaplan; L. Liang; J.L. Min; M.F. Moffatt; C. Molony; G. Nicholson; E.E. Schadt; K.T. Zondervan; M.F. Feitosa; T. Ferreira; H. Lango Allen; R.J. Weyant; E. Wheeler; A.R. Wood; K. Estrada; M.E. Goddard; G. Lettre; M. Mangino; DR Nyholt; S. Purcell; A.V. Smith; H.M. Visscher; J. Yang; S.A. McCarroll; J. Nemesh; B.F. Voight; D. Absher; N. Amin; T. Aspelund; L. Coin; N.L. Glazer; C. Hayward; N.L. Heard-Costa; J.J. Hottenga; A. Johansson; T. Johnson; M. Kaakinen; K. Kapur; S. Ketkar; J.W. Knowles; P. Kraft; A.T. Kraja; C. Lamina; M.F. Leitzmann; B. McKnight; A.P. Morris; K.K. Ong; J.R.B. Perry; M.J. Peters; O. Polasek; I. Prokopenko; N.W. Rayner; S. Ripatti; F. Rivadeneira; R. Robertson; S. Sanna; U. Sovio; I. Surakka; A. Teumer; K.M.C. van Wingerden; V. Vitart; J.H. Zhao; C. Cavalcanti-Proença; P.S. Chines; E. Fisher; J.R. Kulzer; C. Lecoeur; N. Narisu; C. Sandholt; E.J.C. de Geus; G. Willemsen; B.W.J.H. Penninx; K.L. Mohlke; C.M. Lindgren

doi:https://doi.org/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

I.M. Heid, A.U. Jackson, J.C. Randall, T.W. Winkler, L. Qi, V. Steinthorsdottir, G. Thorleifsson, M.C. Zillikens, E.K. Speliotes, R. Mägi, T. Workalemahu, C.C. White, N. Bouatia-Naji, T.B. Harris, S.I. Berndt, E. Ingelsson, C.J. Willer, M.N. Weedon, J. Luan, S. VedantamT. Esko, T.O. Kilpeläinen, Z. Kutalik, S. Li, K.L. Monda, A.L. Dixon, C.C. Holmes, L.M. Kaplan, L. Liang, J.L. Min, M.F. Moffatt, C. Molony, G. Nicholson, E.E. Schadt, K.T. Zondervan, M.F. Feitosa, T. Ferreira, H. Lango Allen, R.J. Weyant, E. Wheeler, A.R. Wood, K. Estrada, M.E. Goddard, G. Lettre, M. Mangino, DR Nyholt, S. Purcell, A.V. Smith, H.M. Visscher, J. Yang, S.A. McCarroll, J. Nemesh, B.F. Voight, D. Absher, N. Amin, T. Aspelund, L. Coin, N.L. Glazer, C. Hayward, N.L. Heard-Costa, J.J. Hottenga, A. Johansson, T. Johnson, M. Kaakinen, K. Kapur, S. Ketkar, J.W. Knowles, P. Kraft, A.T. Kraja, C. Lamina, M.F. Leitzmann, B. McKnight, A.P. Morris, K.K. Ong, J.R.B. Perry, M.J. Peters, O. Polasek, I. Prokopenko, N.W. Rayner, S. Ripatti, F. Rivadeneira, R. Robertson, S. Sanna, U. Sovio, I. Surakka, A. Teumer, K.M.C. van Wingerden, V. Vitart, J.H. Zhao, C. Cavalcanti-Proença, P.S. Chines, E. Fisher, J.R. Kulzer, C. Lecoeur, N. Narisu, C. Sandholt, E.J.C. de Geus, G. Willemsen, B.W.J.H. Penninx, K.L. Mohlke, C.M. Lindgren

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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-SPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9-10-9 to P = 1.8-10-40) 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 = 1.9-10-3 to P = 1.2-10-13). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions. © 2010 Nature America, Inc. All rights reserved.

Original language	English
Pages (from-to)	949-960
Journal	Nature Genetics
Volume	42
Issue number	11
DOIs	https://doi.org/10.1038/ng.685
Publication status	Published - 2010

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Cite this

Heid, I. M., Jackson, A. U., Randall, J. C., Winkler, T. W., Qi, L., Steinthorsdottir, V., Thorleifsson, G., Zillikens, M. C., Speliotes, E. K., Mägi, R., Workalemahu, T., White, C. C., Bouatia-Naji, N., Harris, T. B., Berndt, S. I., Ingelsson, E., Willer, C. J., Weedon, M. N., Luan, J., ... Lindgren, C. M. (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), 949-960. https://doi.org/10.1038/ng.685

@article{ab31537a661f48a2b8c07e0054dc5a13,

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-SPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9-10-9 to P = 1.8-10-40) 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 = 1.9-10-3 to P = 1.2-10-13). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions. {\textcopyright} 2010 Nature America, Inc. All rights reserved.",

author = "I.M. Heid and A.U. Jackson and J.C. Randall and T.W. Winkler and L. Qi and V. Steinthorsdottir and G. Thorleifsson and M.C. Zillikens and E.K. Speliotes and R. M{\"a}gi and T. Workalemahu and C.C. White and N. Bouatia-Naji and T.B. Harris and S.I. Berndt and E. Ingelsson and C.J. Willer and M.N. Weedon and J. Luan and S. Vedantam and T. Esko and T.O. Kilpel{\"a}inen and Z. Kutalik and S. Li and K.L. Monda and A.L. Dixon and C.C. Holmes and L.M. Kaplan and L. Liang and J.L. Min and M.F. Moffatt and C. Molony and G. Nicholson and E.E. Schadt and K.T. Zondervan and M.F. Feitosa and T. Ferreira and {Lango Allen}, H. and R.J. Weyant and E. Wheeler and A.R. Wood and K. Estrada and M.E. Goddard and G. Lettre and M. Mangino and DR Nyholt and S. Purcell and A.V. Smith and H.M. Visscher and J. Yang and S.A. McCarroll and J. Nemesh and B.F. Voight and D. Absher and N. Amin and T. Aspelund and L. Coin and N.L. Glazer and C. Hayward and N.L. Heard-Costa and J.J. Hottenga and A. Johansson and T. Johnson and M. Kaakinen and K. Kapur and S. Ketkar and J.W. Knowles and P. Kraft and A.T. Kraja and C. Lamina and M.F. Leitzmann and B. McKnight and A.P. Morris and K.K. Ong and J.R.B. Perry and M.J. Peters and O. Polasek and I. Prokopenko and N.W. Rayner and S. Ripatti and F. Rivadeneira and R. Robertson and S. Sanna and U. Sovio and I. Surakka and A. Teumer and {van Wingerden}, K.M.C. and V. Vitart and J.H. Zhao and C. Cavalcanti-Proen{\c c}a and P.S. Chines and E. Fisher and J.R. Kulzer and C. Lecoeur and N. Narisu and C. Sandholt and {de Geus}, E.J.C. and G. Willemsen and B.W.J.H. Penninx and K.L. Mohlke and C.M. Lindgren",

year = "2010",

doi = "https://doi.org/10.1038/ng.685",

language = "English",

volume = "42",

pages = "949--960",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "11",

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Heid, IM, Jackson, AU, Randall, JC, Winkler, TW, Qi, L, Steinthorsdottir, V, Thorleifsson, G, Zillikens, MC, Speliotes, EK, Mägi, R, Workalemahu, T, White, CC, Bouatia-Naji, N, Harris, TB, Berndt, SI, Ingelsson, E, Willer, CJ, Weedon, MN, Luan, J, Vedantam, S, Esko, T, Kilpeläinen, TO, Kutalik, Z, Li, S, Monda, KL, Dixon, AL, Holmes, CC, Kaplan, LM, Liang, L, Min, JL, Moffatt, MF, Molony, C, Nicholson, G, Schadt, EE, Zondervan, KT, Feitosa, MF, Ferreira, T, Lango Allen, H, Weyant, RJ, Wheeler, E, Wood, AR, Estrada, K, Goddard, ME, Lettre, G, Mangino, M, Nyholt, DR, Purcell, S, Smith, AV, Visscher, HM, Yang, J, 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, MJ, Polasek, O, Prokopenko, I, Rayner, NW, Ripatti, S, Rivadeneira, F, Robertson, R, Sanna, S, Sovio, U, Surakka, I, Teumer, A, van Wingerden, KMC, Vitart, V, Zhao, JH, Cavalcanti-Proença, C, Chines, PS, Fisher, E, Kulzer, JR, Lecoeur, C, Narisu, N, Sandholt, C, de Geus, EJC, Willemsen, G, Penninx, BWJH, 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. 949-960. 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, I.M.

AU - Jackson, A.U.

AU - Randall, J.C.

AU - Winkler, T.W.

AU - Qi, L.

AU - Steinthorsdottir, V.

AU - Thorleifsson, G.

AU - Zillikens, M.C.

AU - Speliotes, E.K.

AU - Mägi, R.

AU - Workalemahu, T.

AU - White, C.C.

AU - Bouatia-Naji, N.

AU - Harris, T.B.

AU - Berndt, S.I.

AU - Ingelsson, E.

AU - Willer, C.J.

AU - Weedon, M.N.

AU - Luan, J.

AU - Vedantam, S.

AU - Esko, T.

AU - Kilpeläinen, T.O.

AU - Kutalik, Z.

AU - Li, S.

AU - Monda, K.L.

AU - Dixon, A.L.

AU - Holmes, C.C.

AU - Kaplan, L.M.

AU - Liang, L.

AU - Min, J.L.

AU - Moffatt, M.F.

AU - Molony, C.

AU - Nicholson, G.

AU - Schadt, E.E.

AU - Zondervan, K.T.

AU - Feitosa, M.F.

AU - Ferreira, T.

AU - Lango Allen, H.

AU - Weyant, R.J.

AU - Wheeler, E.

AU - Wood, A.R.

AU - Estrada, K.

AU - Goddard, M.E.

AU - Lettre, G.

AU - Mangino, M.

AU - Nyholt, DR

AU - Purcell, S.

AU - Smith, A.V.

AU - Visscher, H.M.

AU - Yang, J.

AU - McCarroll, S.A.

AU - Nemesh, J.

AU - Voight, B.F.

AU - Absher, D.

AU - Amin, N.

AU - Aspelund, T.

AU - Coin, L.

AU - Glazer, N.L.

AU - Hayward, C.

AU - Heard-Costa, N.L.

AU - Hottenga, J.J.

AU - Johansson, A.

AU - Johnson, T.

AU - Kaakinen, M.

AU - Kapur, K.

AU - Ketkar, S.

AU - Knowles, J.W.

AU - Kraft, P.

AU - Kraja, A.T.

AU - Lamina, C.

AU - Leitzmann, M.F.

AU - McKnight, B.

AU - Morris, A.P.

AU - Ong, K.K.

AU - Perry, J.R.B.

AU - Peters, M.J.

AU - Polasek, O.

AU - Prokopenko, I.

AU - Rayner, N.W.

AU - Ripatti, S.

AU - Rivadeneira, F.

AU - Robertson, R.

AU - Sanna, S.

AU - Sovio, U.

AU - Surakka, I.

AU - Teumer, A.

AU - van Wingerden, K.M.C.

AU - Vitart, V.

AU - Zhao, J.H.

AU - Cavalcanti-Proença, C.

AU - Chines, P.S.

AU - Fisher, E.

AU - Kulzer, J.R.

AU - Lecoeur, C.

AU - Narisu, N.

AU - Sandholt, C.

AU - de Geus, E.J.C.

AU - Willemsen, G.

AU - Penninx, B.W.J.H.

AU - Mohlke, K.L.

AU - Lindgren, C.M.

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-SPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9-10-9 to P = 1.8-10-40) 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 = 1.9-10-3 to P = 1.2-10-13). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions. © 2010 Nature America, Inc. All rights reserved.

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-SPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9-10-9 to P = 1.8-10-40) 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 = 1.9-10-3 to P = 1.2-10-13). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions. © 2010 Nature America, Inc. All rights reserved.

U2 - https://doi.org/10.1038/ng.685

DO - https://doi.org/10.1038/ng.685

M3 - Article

C2 - 20935629

SN - 1061-4036

VL - 42

SP - 949

EP - 960

JO - Nature Genetics

JF - Nature Genetics

IS - 11

ER -