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

Iris M. Heid; Anne U. Jackson; Joshua C. Randall; Tthomas W. Winkler; Llu Qi; Valgerdur Ssteinthorsdottir; Ggudmar Tthorleifsson; Ccarola Zillikens; Eelizabeth K. Sspeliotes; Reedik Mägi; Tsegaselassie Workalemahu; Charles White; Nabila Bouatia-Naji; Tamara B. Harris; Ssonja I. Berndt; Eerik Ingelsson; Cristen J. Willer; Michael N. Weedon; Jian'An Luan; Ssailaja Vedantam; Tõnu Eesko; Tuomas O. Kilpeläinen; Zoltán Kutalik; Sshengxu Li; Keri L. Monda; Anna Dixon; Christopher Holmes; Lee Kaplan; Liming Liang; Josine Min; Miriam F. Moffatt; Cliona Molony; Ggeorge Nicholson; Eeric E. Sschadt; Krina T. Zondervan; Mary F. Feitosa; Teresa Ferreira; Hana Lango Allen; Robert J. Weyant; Eeleanor Wheeler; Andrew R. Wood; Magic; Karol Eestrada; Micheal E. Goddard; Guillaume Lettre; Massimo Mangino; Dale R. Nyholt; Sshaun Purcell; Albert Vernon Ssmith; Peter Visscher; Jian Yang; Ssteven A. McCcarroll; James Nemesh; Benjamin F. Voight; Devin Absher; Najaf Amin; Thor Aspelund; Lachlan Coin; Nicole Glazer; Caroline Hayward; Nancy Heard-Ccosta; Jouke Jan Hottenga; Åsa Johansson; Toby Johnson; Marika Kaakinen; Karen Kapur; Sshamika Ketkar; Joshua Knowles; Peter Kraft; Aldi Kraja; Claudia Lamina; Micheal F. Leitzmann; Barbara McKknight; Andrew P. Morris; Ken Oong; John R.B. Perry; Marjolein J. Peters; Oozren Polasek; Inga Prokopenko; Nigel Rayner; Ssamuli Ripatti; Fernando Rivadeneira; Neil R. Robertson; Serena Sanna; Ulla Sovio; Ida Surakka; Alexander Teumer; Sophie Van Wingerden; Veronique Vitart; Jing Hua Zhao; Christine Cavalcanti-Proença; Peter S. Chines; Eeva Fisher; Jennifer R. Kulzer; Cecile Lecoeur; Narisu Narisu; Camilla Sandholt; Laura J. Scott; Kaisa Silander; Klaus Stark; Mari Lliis Tammesoo; Tanya M. Teslovich; Nicholas John Timpson; Richard Watanabe; Ryan Welch; Daniel I. Chasman; Matthew N. Cooper; John Oolov Jansson; Johannes Kettunen; Robert Wlawrence; Niina Pellikka; Markus Perola; Liesbeth Vandenput; Helene Alavere; Peter Almgren; Larry D. Atwood; Amanda J. Bennett; Reiner Biffar; Lori L. Bonnycastle; Stefan R. Bornstein; Thomas A. Buchanan; Harry Campbell; Ian Day; Mariano Dei; Marcus Dörr; Paul Eelliott; Michael R. Eerdos; Johan G. Eeriksson; Nelson B. Freimer; Mao Fu; Stefan Gaget; Eeco J.C. Geus; Anette P. Gjesing; Harald Grallert; Jürgen Gräßler; Christopher J. Groves; Candace Guiducci; Anna Lliisa Hartikainen; Neelam Hassanali; Aki S. Havulinna; Karl Heinz Herzig; Andrew A. Hicks; Jennie Hui; Wilmar Igl; Pekka Jousilahti; Antti Jula; Eeero Kajantie; Leena Kinnunen; Ivana Kolcic; Seppo Koskinen; Peter Kovacs; Heyo K. Kroemer; Vjekoslav Krzelj; Johanna Kuusisto; Kirsti Kvaloy; Jaana Laitinen; Oolivier Lantieri; Mark Lathrop; Marja Llokki Lokki; Robert Luben; Barbara Ludwig; Wendy McArdle; Anne McCcarthy; Mario A. Morken; Mari Nelis; Matt J. Neville; Guillaume Paré; Alex Parker; John F. Peden; Irene Pichler; Kirsi H. Pietiläinen; Carl P. Platou; Anneli Pouta; Martin Ridderstråle; Nilesh J. Samani; Jouko Saramies; Juha Sinisalo; Jan H. Smit; Rona J. Strawbridge; Heather Stringham; Amy J. Swift; Maris Teder-Llaving; Brian Thomson; Gianluca Usala; Joyce B.J. Van Mmeurs; Gert Jan Van Ommen; Vincent Vatin; Claudia B. Volpato; Henri Wallaschofski; Bragi Walters; Eelisabeth Widen; Sarah H. Wild; Gonneke Willemsen; Deniel R. Witte; Lina Zgaga; Paavo Zitting; John P. Beilby; Alan James; Mika Kähönen; Terho Lehtimäki; Markku Nieminen; Claes Ohlsson; Lyle J. Palmer; Olli Raitakari; Paul Ridker; Micheal Stumvoll; Anke Tönjes; Jorma Viikari; Beverley Balkau; Yoav Ben-Shlomo; Richard Bergman; Heiner Boeing; George Ddavey Smith; Shah Eebrahim; Philippe Froguel; Torben Hansen; Christian Hengstenberg; Kristian Hveem; Bo Isomaa; Torben Jørgensen; Fredrik Karpe; Kay Ttee Khaw; Markku Laakso; Debbie A. Lawlor; Michel Marre; Thomas Meitinger; Andres Metspalu; Kristian Midthjell; Oluf Pedersen; Veikko Salomaa; Peter Ee H. Schwarz; Tiinamaija Tuomi; Jaakko Tuomilehto; Timo T. Valle; Nicholas J. Wareham; Alice Arnold; Jacques Beckmann; Sven Bergmann; Eeric Boerwinkle; Dorret I. Boomsma; Mark J. Caulfield; Francis Collins; Gudny Eeiriksdottir; Vilmundur Gudnason; Ulf Gyllensten; Anders Hamsten; Andrew Hattersley; Albert Hofman; Frank B. Hu; Thomas Illig; Carlos Iribarren; Marjo Riitta Jarvelin; W. H.Linda Kao; Jaakko Kaprio; Lenore J. Launer; Patricia B. Munroe; Ben Oostra; Brenda Penninx; Peter P. Pramstaller; Bruce Psaty; Thomas Quertermous; Aila Rissanen; Igor Rudan; Alan R. Shuldiner; Nicole Soranzo; Timothy Spector; Ann Cchristine Syvanen; Manuela Uda; André Uitterlinden; Henry Völzke; Peter Vollenweider; James F. Wilson; Jacqueline Witteman; Alan F. Wright; Gonçalo R. Abecasis; Micheal Boehnke; Ingrid B. Borecki; Panos Deloukas; Timothy M. Frayling; Leif Groop; Talin Haritunians; David J. Hunter; Robert Kaplan; Kari North; Jeffrey R. O'Cconnell; Leena Peltonen; David Schlessinger; David P. Strachan; Joel Hirschhorn; Themistocles Assimes; H. Eerich Wichmann; Unnur Thorsteinsdottir; Cornelia Van Dduijn; Kari Stefansson; Adrienne Cupples; Ruth J.F. Loos; Inês Barroso; Mark I. McCcarthy; Caroline Fox; Karen Mohlke; Cecilia 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

Iris M. Heid, Anne U. Jackson, Joshua C. Randall, Tthomas W. Winkler, Llu Qi, Valgerdur Ssteinthorsdottir, Ggudmar Tthorleifsson, Ccarola Zillikens, Eelizabeth K. Sspeliotes, Reedik Mägi, Tsegaselassie Workalemahu, Charles White, Nabila Bouatia-Naji, Tamara B. Harris, Ssonja I. Berndt, Eerik Ingelsson, Cristen J. Willer, Michael N. Weedon, Jian'An Luan, Ssailaja VedantamTõnu Eesko, Tuomas O. Kilpeläinen, Zoltán Kutalik, Sshengxu Li, Keri L. Monda, Anna Dixon, Christopher Holmes, Lee Kaplan, Liming Liang, Josine Min, Miriam F. Moffatt, Cliona Molony, Ggeorge Nicholson, Eeric E. Sschadt, Krina T. Zondervan, Mary F. Feitosa, Teresa Ferreira, Hana Lango Allen, Robert J. Weyant, Eeleanor Wheeler, Andrew R. Wood, Magic, Karol Eestrada, Micheal E. Goddard, Guillaume Lettre, Massimo Mangino, Dale R. Nyholt, Sshaun Purcell, Albert Vernon Ssmith, Peter Visscher, Jian Yang, Ssteven A. McCcarroll, James Nemesh, Benjamin F. Voight, Devin Absher, Najaf Amin, Thor Aspelund, Lachlan Coin, Nicole Glazer, Caroline Hayward, Nancy Heard-Ccosta, Jouke Jan Hottenga, Åsa Johansson, Toby Johnson, Marika Kaakinen, Karen Kapur, Sshamika Ketkar, Joshua Knowles, Peter Kraft, Aldi Kraja, Claudia Lamina, Micheal F. Leitzmann, Barbara McKknight, Andrew P. Morris, Ken Oong, John R.B. Perry, Marjolein J. Peters, Oozren Polasek, Inga Prokopenko, Nigel Rayner, Ssamuli Ripatti, Fernando Rivadeneira, Neil R. Robertson, Serena Sanna, Ulla Sovio, Ida Surakka, Alexander Teumer, Sophie Van Wingerden, Veronique Vitart, Jing Hua Zhao, Christine Cavalcanti-Proença, Peter S. Chines, Eeva Fisher, Jennifer R. Kulzer, Cecile Lecoeur, Narisu Narisu, Camilla Sandholt, Laura J. Scott, Kaisa Silander, Klaus Stark, Mari Lliis Tammesoo, Tanya M. Teslovich, Nicholas John Timpson, Richard Watanabe, Ryan Welch, Daniel I. Chasman, Matthew N. Cooper, John Oolov Jansson, Johannes Kettunen, Robert Wlawrence, Niina Pellikka, Markus Perola, Liesbeth Vandenput, Helene Alavere, Peter Almgren, Larry D. Atwood, Amanda J. Bennett, Reiner Biffar, Lori L. Bonnycastle, Stefan R. Bornstein, Thomas A. Buchanan, Harry Campbell, Ian Day, Mariano Dei, Marcus Dörr, Paul Eelliott, Michael R. Eerdos, Johan G. Eeriksson, Nelson B. Freimer, Mao Fu, Stefan Gaget, Eeco J.C. Geus, Anette P. Gjesing, Harald Grallert, Jürgen Gräßler, Christopher J. Groves, Candace Guiducci, Anna Lliisa Hartikainen, Neelam Hassanali, Aki S. Havulinna, Karl Heinz Herzig, Andrew A. Hicks, Jennie Hui, Wilmar Igl, Pekka Jousilahti, Antti Jula, Eeero Kajantie, Leena Kinnunen, Ivana Kolcic, Seppo Koskinen, Peter Kovacs, Heyo K. Kroemer, Vjekoslav Krzelj, Johanna Kuusisto, Kirsti Kvaloy, Jaana Laitinen, Oolivier Lantieri, Mark Lathrop, Marja Llokki Lokki, Robert Luben, Barbara Ludwig, Wendy McArdle, Anne McCcarthy, Mario A. Morken, Mari Nelis, Matt J. Neville, Guillaume Paré, Alex Parker, John F. Peden, Irene Pichler, Kirsi H. Pietiläinen, Carl P. Platou, Anneli Pouta, Martin Ridderstråle, Nilesh J. Samani, Jouko Saramies, Juha Sinisalo, Jan H. Smit, Rona J. Strawbridge, Heather Stringham, Amy J. Swift, Maris Teder-Llaving, Brian Thomson, Gianluca Usala, Joyce B.J. Van Mmeurs, Gert Jan Van Ommen, Vincent Vatin, Claudia B. Volpato, Henri Wallaschofski, Bragi Walters, Eelisabeth Widen, Sarah H. Wild, Gonneke Willemsen, Deniel R. Witte, Lina Zgaga, Paavo Zitting, John P. Beilby, Alan James, Mika Kähönen, Terho Lehtimäki, Markku Nieminen, Claes Ohlsson, Lyle J. Palmer, Olli Raitakari, Paul Ridker, Micheal Stumvoll, Anke Tönjes, Jorma Viikari, Beverley Balkau, Yoav Ben-Shlomo, Richard Bergman, Heiner Boeing, George Ddavey Smith, Shah Eebrahim, Philippe Froguel, Torben Hansen, Christian Hengstenberg, Kristian Hveem, Bo Isomaa, Torben Jørgensen, Fredrik Karpe, Kay Ttee Khaw, Markku Laakso, Debbie A. Lawlor, Michel Marre, Thomas Meitinger, Andres Metspalu, Kristian Midthjell, Oluf Pedersen, Veikko Salomaa, Peter Ee H. Schwarz, Tiinamaija Tuomi, Jaakko Tuomilehto, Timo T. Valle, Nicholas J. Wareham, Alice Arnold, Jacques Beckmann, Sven Bergmann, Eeric Boerwinkle, Dorret I. Boomsma, Mark J. Caulfield, Francis Collins, Gudny Eeiriksdottir, Vilmundur Gudnason, Ulf Gyllensten, Anders Hamsten, Andrew Hattersley, Albert Hofman, Frank B. Hu, Thomas Illig, Carlos Iribarren, Marjo Riitta Jarvelin, W. H.Linda Kao, Jaakko Kaprio, Lenore J. Launer, Patricia B. Munroe, Ben Oostra, Brenda Penninx, Peter P. Pramstaller, Bruce Psaty, Thomas Quertermous, Aila Rissanen, Igor Rudan, Alan R. Shuldiner, Nicole Soranzo, Timothy Spector, Ann Cchristine Syvanen, Manuela Uda, André Uitterlinden, Henry Völzke, Peter Vollenweider, James F. Wilson, Jacqueline Witteman, Alan F. Wright, Gonçalo R. Abecasis, Micheal Boehnke, Ingrid B. Borecki, Panos Deloukas, Timothy M. Frayling, Leif Groop, Talin Haritunians, David J. Hunter, Robert Kaplan, Kari North, Jeffrey R. O'Cconnell, Leena Peltonen, David Schlessinger, David P. Strachan, Joel Hirschhorn, Themistocles Assimes, H. Eerich Wichmann, Unnur Thorsteinsdottir, Cornelia Van Dduijn, Kari Stefansson, Adrienne Cupples, Ruth J.F. Loos, Inês Barroso, Mark I. McCcarthy, Caroline Fox, Karen Mohlke, Cecilia Lindgren

Division of Cardiology

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784 Scopus citations

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.

Original language	English
Pages (from-to)	949-960
Number of pages	12
Journal	Nature Genetics
Volume	42
Issue number	11
DOIs	https://doi.org/10.1038/ng.685
State	Published - Nov 1 2010

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10.1038/ng.685

Cite this

Heid, I. M., Jackson, A. U., Randall, J. C., Winkler, T. W., Qi, L., Ssteinthorsdottir, V., Tthorleifsson, G., Zillikens, C., Sspeliotes, E. K., Mägi, R., Workalemahu, T., White, C., Bouatia-Naji, N., Harris, T. B., Berndt, S. I., Ingelsson, E., Willer, C. J., Weedon, M. N., Luan, JA., ... Lindgren, C. (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{eddc8a16a25649d4926396f3b47f4b14,

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.",

author = "Heid, {Iris M.} and Jackson, {Anne U.} and Randall, {Joshua C.} and Winkler, {Tthomas W.} and Llu Qi and Valgerdur Ssteinthorsdottir and Ggudmar Tthorleifsson and Ccarola Zillikens and Sspeliotes, {Eelizabeth K.} and Reedik M{\"a}gi and Tsegaselassie Workalemahu and Charles White and Nabila Bouatia-Naji and Harris, {Tamara B.} and Berndt, {Ssonja I.} and Eerik Ingelsson and Willer, {Cristen J.} and Weedon, {Michael N.} and Jian'An Luan and Ssailaja Vedantam and T{\~o}nu Eesko and Kilpel{\"a}inen, {Tuomas O.} and Zolt{\'a}n Kutalik and Sshengxu Li and Monda, {Keri L.} and Anna Dixon and Christopher Holmes and Lee Kaplan and Liming Liang and Josine Min and Moffatt, {Miriam F.} and Cliona Molony and Ggeorge Nicholson and Sschadt, {Eeric E.} and Zondervan, {Krina T.} and Feitosa, {Mary F.} and Teresa Ferreira and Allen, {Hana Lango} and Weyant, {Robert J.} and Eeleanor Wheeler and Wood, {Andrew R.} and Magic and Karol Eestrada and Goddard, {Micheal E.} and Guillaume Lettre and Massimo Mangino and Nyholt, {Dale R.} and Sshaun Purcell and Ssmith, {Albert Vernon} and Peter Visscher and Jian Yang and McCcarroll, {Ssteven A.} and James Nemesh and Voight, {Benjamin F.} and Devin Absher and Najaf Amin and Thor Aspelund and Lachlan Coin and Nicole Glazer and Caroline Hayward and Nancy Heard-Ccosta and Hottenga, {Jouke Jan} and {\AA}sa Johansson and Toby Johnson and Marika Kaakinen and Karen Kapur and Sshamika Ketkar and Joshua Knowles and Peter Kraft and Aldi Kraja and Claudia Lamina and Leitzmann, {Micheal F.} and Barbara McKknight and Morris, {Andrew P.} and Ken Oong and Perry, {John R.B.} and Peters, {Marjolein J.} and Oozren Polasek and Inga Prokopenko and Nigel Rayner and Ssamuli Ripatti and Fernando Rivadeneira and Robertson, {Neil R.} and Serena Sanna and Ulla Sovio and Ida Surakka and Alexander Teumer and {Van Wingerden}, Sophie and Veronique Vitart and Zhao, {Jing Hua} and Christine Cavalcanti-Proen{\c c}a and Chines, {Peter S.} and Eeva Fisher and Kulzer, {Jennifer R.} and Cecile Lecoeur and Narisu Narisu and Camilla Sandholt and Scott, {Laura J.} and Kaisa Silander and Klaus Stark and Tammesoo, {Mari Lliis} and Teslovich, {Tanya M.} and Timpson, {Nicholas John} and Richard Watanabe and Ryan Welch and Chasman, {Daniel I.} and Cooper, {Matthew N.} and Jansson, {John Oolov} and Johannes Kettunen and Robert Wlawrence and Niina Pellikka and Markus Perola and Liesbeth Vandenput and Helene Alavere and Peter Almgren and Atwood, {Larry D.} and Bennett, {Amanda J.} and Reiner Biffar and Bonnycastle, {Lori L.} and Bornstein, {Stefan R.} and Buchanan, {Thomas A.} and Harry Campbell and Ian Day and Mariano Dei and Marcus D{\"o}rr and Paul Eelliott and Eerdos, {Michael R.} and Eeriksson, {Johan G.} and Freimer, {Nelson B.} and Mao Fu and Stefan Gaget and Geus, {Eeco J.C.} and Gjesing, {Anette P.} and Harald Grallert and J{\"u}rgen Gr{\"a}{\ss}ler and Groves, {Christopher J.} and Candace Guiducci and Hartikainen, {Anna Lliisa} and Neelam Hassanali and Havulinna, {Aki S.} and Herzig, {Karl Heinz} and Hicks, {Andrew A.} and Jennie Hui and Wilmar Igl and Pekka Jousilahti and Antti Jula and Eeero Kajantie and Leena Kinnunen and Ivana Kolcic and Seppo Koskinen and Peter Kovacs and Kroemer, {Heyo K.} and Vjekoslav Krzelj and Johanna Kuusisto and Kirsti Kvaloy and Jaana Laitinen and Oolivier Lantieri and Mark Lathrop and Lokki, {Marja Llokki} and Robert Luben and Barbara Ludwig and Wendy McArdle and Anne McCcarthy and Morken, {Mario A.} and Mari Nelis and Neville, {Matt J.} and Guillaume Par{\'e} and Alex Parker and Peden, {John F.} and Irene Pichler and Pietil{\"a}inen, {Kirsi H.} and Platou, {Carl P.} and Anneli Pouta and Martin Ridderstr{\aa}le and Samani, {Nilesh J.} and Jouko Saramies and Juha Sinisalo and Smit, {Jan H.} and Strawbridge, {Rona J.} and Heather Stringham and Swift, {Amy J.} and Maris Teder-Llaving and Brian Thomson and Gianluca Usala and {Van Mmeurs}, {Joyce B.J.} and {Van Ommen}, {Gert Jan} and Vincent Vatin and Volpato, {Claudia B.} and Henri Wallaschofski and Bragi Walters and Eelisabeth Widen and Wild, {Sarah H.} and Gonneke Willemsen and Witte, {Deniel R.} and Lina Zgaga and Paavo Zitting and Beilby, {John P.} and Alan James and Mika K{\"a}h{\"o}nen and Terho Lehtim{\"a}ki and Markku Nieminen and Claes Ohlsson and Palmer, {Lyle J.} and Olli Raitakari and Paul Ridker and Micheal Stumvoll and Anke T{\"o}njes and Jorma Viikari and Beverley Balkau and Yoav Ben-Shlomo and Richard Bergman and Heiner Boeing and Smith, {George Ddavey} and Shah Eebrahim and Philippe Froguel and Torben Hansen and Christian Hengstenberg and Kristian Hveem and Bo Isomaa and Torben J{\o}rgensen and Fredrik Karpe and Khaw, {Kay Ttee} and Markku Laakso and Lawlor, {Debbie A.} and Michel Marre and Thomas Meitinger and Andres Metspalu and Kristian Midthjell and Oluf Pedersen and Veikko Salomaa and Schwarz, {Peter Ee H.} and Tiinamaija Tuomi and Jaakko Tuomilehto and Valle, {Timo T.} and Wareham, {Nicholas J.} and Alice Arnold and Jacques Beckmann and Sven Bergmann and Eeric Boerwinkle and Boomsma, {Dorret I.} and Caulfield, {Mark J.} and Francis Collins and Gudny Eeiriksdottir and Vilmundur Gudnason and Ulf Gyllensten and Anders Hamsten and Andrew Hattersley and Albert Hofman and Hu, {Frank B.} and Thomas Illig and Carlos Iribarren and Jarvelin, {Marjo Riitta} and Kao, {W. H.Linda} and Jaakko Kaprio and Launer, {Lenore J.} and Munroe, {Patricia B.} and Ben Oostra and Brenda Penninx and Pramstaller, {Peter P.} and Bruce Psaty and Thomas Quertermous and Aila Rissanen and Igor Rudan and Shuldiner, {Alan R.} and Nicole Soranzo and Timothy Spector and Syvanen, {Ann Cchristine} and Manuela Uda and Andr{\'e} Uitterlinden and Henry V{\"o}lzke and Peter Vollenweider and Wilson, {James F.} and Jacqueline Witteman and Wright, {Alan F.} and Abecasis, {Gon{\c c}alo R.} and Micheal Boehnke and Borecki, {Ingrid B.} and Panos Deloukas and Frayling, {Timothy M.} and Leif Groop and Talin Haritunians and Hunter, {David J.} and Robert Kaplan and Kari North and O'Cconnell, {Jeffrey R.} and Leena Peltonen and David Schlessinger and Strachan, {David P.} and Joel Hirschhorn and Themistocles Assimes and Wichmann, {H. Eerich} and Unnur Thorsteinsdottir and {Van Dduijn}, Cornelia and Kari Stefansson and Adrienne Cupples and Loos, {Ruth J.F.} and In{\^e}s Barroso and McCcarthy, {Mark I.} and Caroline Fox and Karen Mohlke and Cecilia Lindgren",

year = "2010",

month = nov,

day = "1",

doi = "10.1038/ng.685",

language = "English",

volume = "42",

pages = "949--960",

journal = "Nature Genetics",

issn = "1061-4036",

number = "11",

}

Heid, IM, Jackson, AU, Randall, JC, Winkler, TW, Qi, L, Ssteinthorsdottir, V, Tthorleifsson, G, Zillikens, C, Sspeliotes, EK, Mägi, R, Workalemahu, T, White, C, Bouatia-Naji, N, Harris, TB, Berndt, SI, Ingelsson, E, Willer, CJ, Weedon, MN, Luan, JA, Vedantam, S, Eesko, T, Kilpeläinen, TO, Kutalik, Z, Li, S, Monda, KL, Dixon, A, Holmes, C, Kaplan, L, Liang, L, Min, J, Moffatt, MF, Molony, C, Nicholson, G, Sschadt, EE, Zondervan, KT, Feitosa, MF, Ferreira, T, Allen, HL, Weyant, RJ, Wheeler, E, Wood, AR, Magic, Eestrada, K, Goddard, ME, Lettre, G, Mangino, M, Nyholt, DR, Purcell, S, Ssmith, AV, Visscher, P, Yang, J, McCcarroll, SA, Nemesh, J, Voight, BF, Absher, D, Amin, N, Aspelund, T, Coin, L, Glazer, N, Hayward, C, Heard-Ccosta, N, Hottenga, JJ, Johansson, Å, Johnson, T, Kaakinen, M, Kapur, K, Ketkar, S, Knowles, J, Kraft, P, Kraja, A, Lamina, C, Leitzmann, MF, McKknight, B, Morris, AP, Oong, K, Perry, JRB, Peters, MJ, Polasek, O, Prokopenko, I, Rayner, N, Ripatti, S, Rivadeneira, F, Robertson, NR, Sanna, S, Sovio, U, Surakka, I, Teumer, A, Van Wingerden, S, Vitart, V, Zhao, JH, Cavalcanti-Proença, 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, R, Welch, R, Chasman, DI, Cooper, MN, Jansson, JO, Kettunen, J, Wlawrence, R, 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, I, Dei, M, Dörr, M, Eelliott, P, Eerdos, MR, Eeriksson, JG, Freimer, NB, Fu, M, Gaget, S, Geus, EJC, Gjesing, AP, Grallert, H, Gräßler, J, Groves, CJ, Guiducci, C, Hartikainen, AL, Hassanali, N, Havulinna, AS, Herzig, KH, Hicks, AA, Hui, J, 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, M, Lokki, ML, Luben, R, Ludwig, B, McArdle, W, McCcarthy, A, Morken, MA, Nelis, M, Neville, MJ, Paré, G, Parker, A, Peden, JF, Pichler, I, Pietiläinen, KH, Platou, CP, Pouta, A, Ridderstråle, M, Samani, NJ, Saramies, J, Sinisalo, J, Smit, JH, Strawbridge, RJ, Stringham, H, Swift, AJ, Teder-Llaving, M, Thomson, B, Usala, G, Van Mmeurs, JBJ, Van Ommen, GJ, Vatin, V, Volpato, CB, Wallaschofski, H, Walters, B, Widen, E, Wild, SH, Willemsen, G, Witte, DR, Zgaga, L, Zitting, P, Beilby, JP, James, A, Kähönen, M, Lehtimäki, T, Nieminen, M, Ohlsson, C, Palmer, LJ, Raitakari, O, Ridker, P, Stumvoll, M, Tönjes, A, Viikari, J, Balkau, B, Ben-Shlomo, Y, Bergman, R, Boeing, H, Smith, GD, Eebrahim, S, Froguel, P, Hansen, T, Hengstenberg, C, Hveem, K, Isomaa, B, Jørgensen, 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, A, Beckmann, J, Bergmann, S, Boerwinkle, E, Boomsma, DI, Caulfield, MJ, Collins, F, Eeiriksdottir, G, Gudnason, V, Gyllensten, U, Hamsten, A, Hattersley, A, Hofman, A, Hu, FB, Illig, T, Iribarren, C, Jarvelin, MR, Kao, WHL, Kaprio, J, Launer, LJ, Munroe, PB, Oostra, B, Penninx, B, Pramstaller, PP, Psaty, B, Quertermous, T, Rissanen, A, Rudan, I, Shuldiner, AR, Soranzo, N, Spector, T, Syvanen, AC, Uda, M, Uitterlinden, A, Völzke, H, Vollenweider, P, Wilson, JF, Witteman, J, Wright, AF, Abecasis, GR, Boehnke, M, Borecki, IB, Deloukas, P, Frayling, TM, Groop, L, Haritunians, T, Hunter, DJ, Kaplan, R, North, K, O'Cconnell, JR, Peltonen, L, Schlessinger, D, Strachan, DP, Hirschhorn, J, Assimes, T, Wichmann, HE, Thorsteinsdottir, U, Van Dduijn, C, Stefansson, K, Cupples, A, Loos, RJF, Barroso, I, McCcarthy, MI, Fox, C, Mohlke, K & Lindgren, C 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, Iris M.

AU - Jackson, Anne U.

AU - Randall, Joshua C.

AU - Winkler, Tthomas W.

AU - Qi, Llu

AU - Ssteinthorsdottir, Valgerdur

AU - Tthorleifsson, Ggudmar

AU - Zillikens, Ccarola

AU - Sspeliotes, Eelizabeth K.

AU - Mägi, Reedik

AU - Workalemahu, Tsegaselassie

AU - White, Charles

AU - Bouatia-Naji, Nabila

AU - Harris, Tamara B.

AU - Berndt, Ssonja I.

AU - Ingelsson, Eerik

AU - Willer, Cristen J.

AU - Weedon, Michael N.

AU - Luan, Jian'An

AU - Vedantam, Ssailaja

AU - Eesko, Tõnu

AU - Kilpeläinen, Tuomas O.

AU - Kutalik, Zoltán

AU - Li, Sshengxu

AU - Monda, Keri L.

AU - Dixon, Anna

AU - Holmes, Christopher

AU - Kaplan, Lee

AU - Liang, Liming

AU - Min, Josine

AU - Moffatt, Miriam F.

AU - Molony, Cliona

AU - Nicholson, Ggeorge

AU - Sschadt, Eeric E.

AU - Zondervan, Krina T.

AU - Feitosa, Mary F.

AU - Ferreira, Teresa

AU - Allen, Hana Lango

AU - Weyant, Robert J.

AU - Wheeler, Eeleanor

AU - Wood, Andrew R.

AU - Magic,

AU - Eestrada, Karol

AU - Goddard, Micheal E.

AU - Lettre, Guillaume

AU - Mangino, Massimo

AU - Nyholt, Dale R.

AU - Purcell, Sshaun

AU - Ssmith, Albert Vernon

AU - Visscher, Peter

AU - Yang, Jian

AU - McCcarroll, Ssteven A.

AU - Nemesh, James

AU - Voight, Benjamin F.

AU - Absher, Devin

AU - Amin, Najaf

AU - Aspelund, Thor

AU - Coin, Lachlan

AU - Glazer, Nicole

AU - Hayward, Caroline

AU - Heard-Ccosta, Nancy

AU - Hottenga, Jouke Jan

AU - Johansson, Åsa

AU - Johnson, Toby

AU - Kaakinen, Marika

AU - Kapur, Karen

AU - Ketkar, Sshamika

AU - Knowles, Joshua

AU - Kraft, Peter

AU - Kraja, Aldi

AU - Lamina, Claudia

AU - Leitzmann, Micheal F.

AU - McKknight, Barbara

AU - Morris, Andrew P.

AU - Oong, Ken

AU - Perry, John R.B.

AU - Peters, Marjolein J.

AU - Polasek, Oozren

AU - Prokopenko, Inga

AU - Rayner, Nigel

AU - Ripatti, Ssamuli

AU - Rivadeneira, Fernando

AU - Robertson, Neil R.

AU - Sanna, Serena

AU - Sovio, Ulla

AU - Surakka, Ida

AU - Teumer, Alexander

AU - Van Wingerden, Sophie

AU - Vitart, Veronique

AU - Zhao, Jing Hua

AU - Cavalcanti-Proença, Christine

AU - Chines, Peter S.

AU - Fisher, Eeva

AU - Kulzer, Jennifer R.

AU - Lecoeur, Cecile

AU - Narisu, Narisu

AU - Sandholt, Camilla

AU - Scott, Laura J.

AU - Silander, Kaisa

AU - Stark, Klaus

AU - Tammesoo, Mari Lliis

AU - Teslovich, Tanya M.

AU - Timpson, Nicholas John

AU - Watanabe, Richard

AU - Welch, Ryan

AU - Chasman, Daniel I.

AU - Cooper, Matthew N.

AU - Jansson, John Oolov

AU - Kettunen, Johannes

AU - Wlawrence, Robert

AU - Pellikka, Niina

AU - Perola, Markus

AU - Vandenput, Liesbeth

AU - Alavere, Helene

AU - Almgren, Peter

AU - Atwood, Larry D.

AU - Bennett, Amanda J.

AU - Biffar, Reiner

AU - Bonnycastle, Lori L.

AU - Bornstein, Stefan R.

AU - Buchanan, Thomas A.

AU - Campbell, Harry

AU - Day, Ian

AU - Dei, Mariano

AU - Dörr, Marcus

AU - Eelliott, Paul

AU - Eerdos, Michael R.

AU - Eeriksson, Johan G.

AU - Freimer, Nelson B.

AU - Fu, Mao

AU - Gaget, Stefan

AU - Geus, Eeco J.C.

AU - Gjesing, Anette P.

AU - Grallert, Harald

AU - Gräßler, Jürgen

AU - Groves, Christopher J.

AU - Guiducci, Candace

AU - Hartikainen, Anna Lliisa

AU - Hassanali, Neelam

AU - Havulinna, Aki S.

AU - Herzig, Karl Heinz

AU - Hicks, Andrew A.

AU - Hui, Jennie

AU - Igl, Wilmar

AU - Jousilahti, Pekka

AU - Jula, Antti

AU - Kajantie, Eeero

AU - Kinnunen, Leena

AU - Kolcic, Ivana

AU - Koskinen, Seppo

AU - Kovacs, Peter

AU - Kroemer, Heyo K.

AU - Krzelj, Vjekoslav

AU - Kuusisto, Johanna

AU - Kvaloy, Kirsti

AU - Laitinen, Jaana

AU - Lantieri, Oolivier

AU - Lathrop, Mark

AU - Lokki, Marja Llokki

AU - Luben, Robert

AU - Ludwig, Barbara

AU - McArdle, Wendy

AU - McCcarthy, Anne

AU - Morken, Mario A.

AU - Nelis, Mari

AU - Neville, Matt J.

AU - Paré, Guillaume

AU - Parker, Alex

AU - Peden, John F.

AU - Pichler, Irene

AU - Pietiläinen, Kirsi H.

AU - Platou, Carl P.

AU - Pouta, Anneli

AU - Ridderstråle, Martin

AU - Samani, Nilesh J.

AU - Saramies, Jouko

AU - Sinisalo, Juha

AU - Smit, Jan H.

AU - Strawbridge, Rona J.

AU - Stringham, Heather

AU - Swift, Amy J.

AU - Teder-Llaving, Maris

AU - Thomson, Brian

AU - Usala, Gianluca

AU - Van Mmeurs, Joyce B.J.

AU - Van Ommen, Gert Jan

AU - Vatin, Vincent

AU - Volpato, Claudia B.

AU - Wallaschofski, Henri

AU - Walters, Bragi

AU - Widen, Eelisabeth

AU - Wild, Sarah H.

AU - Willemsen, Gonneke

AU - Witte, Deniel R.

AU - Zgaga, Lina

AU - Zitting, Paavo

AU - Beilby, John P.

AU - James, Alan

AU - Kähönen, Mika

AU - Lehtimäki, Terho

AU - Nieminen, Markku

AU - Ohlsson, Claes

AU - Palmer, Lyle J.

AU - Raitakari, Olli

AU - Ridker, Paul

AU - Stumvoll, Micheal

AU - Tönjes, Anke

AU - Viikari, Jorma

AU - Balkau, Beverley

AU - Ben-Shlomo, Yoav

AU - Bergman, Richard

AU - Boeing, Heiner

AU - Smith, George Ddavey

AU - Eebrahim, Shah

AU - Froguel, Philippe

AU - Hansen, Torben

AU - Hengstenberg, Christian

AU - Hveem, Kristian

AU - Isomaa, Bo

AU - Jørgensen, Torben

AU - Karpe, Fredrik

AU - Khaw, Kay Ttee

AU - Laakso, Markku

AU - Lawlor, Debbie A.

AU - Marre, Michel

AU - Meitinger, Thomas

AU - Metspalu, Andres

AU - Midthjell, Kristian

AU - Pedersen, Oluf

AU - Salomaa, Veikko

AU - Schwarz, Peter Ee H.

AU - Tuomi, Tiinamaija

AU - Tuomilehto, Jaakko

AU - Valle, Timo T.

AU - Wareham, Nicholas J.

AU - Arnold, Alice

AU - Beckmann, Jacques

AU - Bergmann, Sven

AU - Boerwinkle, Eeric

AU - Boomsma, Dorret I.

AU - Caulfield, Mark J.

AU - Collins, Francis

AU - Eeiriksdottir, Gudny

AU - Gudnason, Vilmundur

AU - Gyllensten, Ulf

AU - Hamsten, Anders

AU - Hattersley, Andrew

AU - Hofman, Albert

AU - Hu, Frank B.

AU - Illig, Thomas

AU - Iribarren, Carlos

AU - Jarvelin, Marjo Riitta

AU - Kao, W. H.Linda

AU - Kaprio, Jaakko

AU - Launer, Lenore J.

AU - Munroe, Patricia B.

AU - Oostra, Ben

AU - Penninx, Brenda

AU - Pramstaller, Peter P.

AU - Psaty, Bruce

AU - Quertermous, Thomas

AU - Rissanen, Aila

AU - Rudan, Igor

AU - Shuldiner, Alan R.

AU - Soranzo, Nicole

AU - Spector, Timothy

AU - Syvanen, Ann Cchristine

AU - Uda, Manuela

AU - Uitterlinden, André

AU - Völzke, Henry

AU - Vollenweider, Peter

AU - Wilson, James F.

AU - Witteman, Jacqueline

AU - Wright, Alan F.

AU - Abecasis, Gonçalo R.

AU - Boehnke, Micheal

AU - Borecki, Ingrid B.

AU - Deloukas, Panos

AU - Frayling, Timothy M.

AU - Groop, Leif

AU - Haritunians, Talin

AU - Hunter, David J.

AU - Kaplan, Robert

AU - North, Kari

AU - O'Cconnell, Jeffrey R.

AU - Peltonen, Leena

AU - Schlessinger, David

AU - Strachan, David P.

AU - Hirschhorn, Joel

AU - Assimes, Themistocles

AU - Wichmann, H. Eerich

AU - Thorsteinsdottir, Unnur

AU - Van Dduijn, Cornelia

AU - Stefansson, Kari

AU - Cupples, Adrienne

AU - Loos, Ruth J.F.

AU - Barroso, Inês

AU - McCcarthy, Mark I.

AU - Fox, Caroline

AU - Mohlke, Karen

AU - Lindgren, Cecilia

PY - 2010/11/1

Y1 - 2010/11/1

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.

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.

UR - http://www.scopus.com/inward/record.url?scp=78049349396&partnerID=8YFLogxK

U2 - 10.1038/ng.685

DO - 10.1038/ng.685

M3 - Article

C2 - 20935629

AN - SCOPUS:78049349396

SN - 1061-4036

VL - 42

SP - 949

EP - 960

JO - Nature Genetics

JF - Nature Genetics

IS - 11

ER -

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

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