Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture

Sonja I Berndt; Stefan Gustafsson; Reedik Mägi; Andrea Ganna; Eleanor Wheeler; Mary F Feitosa; Anne E Justice; Keri L Monda; Damien C Croteau-Chonka; Felix R Day; Tõnu Esko; Tove Fall; Teresa Ferreira; Davide Gentilini; Anne U Jackson; Jian'an Luan; Joshua C Randall; Sailaja Vedantam; Cristen J Willer; Thomas Winkler; Andrew R Wood; Tsegaselassie Workalemahu; Yi-Juan Hu; Sang Hong Lee; Liming Liang; Dan-Yu Lin; Josine L Min; Benjamin M Neale; Gudmar Thorleifsson; Jian Yang; Eva Albrecht; Najaf Amin; Jennifer L Bragg-Gresham; Gemma Cadby; Martin den Heijer; Niina Eklund; Krista Fischer; Anuj Goel; Jouke-Jan Hottenga; Jennifer E Huffman; Ivonne Jarick; Åsa Johansson; Toby Johnson; Stavroula Kanoni; Marcus E Kleber; Inke R König; Kati Kristiansson; Zoltán Kutalik; Claudia Lamina; Cecile Lecoeur; Guo Li; Massimo Mangino; Wendy L McArdle; Carolina Medina-Gomez; Martina Müller-Nurasyid; Julius S Ngwa; Ilja M Nolte; Lavinia Paternoster; Sonali Pechlivanis; Markus Perola; Marjolein J Peters; Michael Preuss; Lynda M Rose; Jianxin Shi; Dmitry Shungin; Albert Vernon Smith; Rona J Strawbridge; Ida Surakka; Alexander Teumer; Mieke D Trip; Jonathan Tyrer; Jana V Van Vliet-Ostaptchouk; Liesbeth Vandenput; Lindsay L Waite; Jing Hua Zhao; Devin Absher; Folkert W Asselbergs; Mustafa Atalay; Antony P Attwood; Anthony J Balmforth; Hanneke Basart; John Beilby; Lori L Bonnycastle; Paolo Brambilla; Marcel Bruinenberg; Harry Campbell; Daniel I Chasman; Peter S Chines; Francis S Collins; John M Connell; William O Cookson; Ulf de Faire; Femmie de Vegt; Mariano Dei; Maria Dimitriou; Sarah Edkins; Karol Estrada; David M Evans; Martin Farrall; Marco M Ferrario; Jean Ferrières; Lude Franke; Francesca Frau; Pablo V Gejman; Harald Grallert; Henrik Grönberg; Vilmundur Gudnason; Alistair S Hall; Per Hall; Anna-Liisa Hartikainen; Caroline Hayward; Nancy L Heard-Costa; Andrew C Heath; Johannes Hebebrand; Georg Homuth; Frank B Hu; Sarah E Hunt; Elina Hyppönen; Carlos Iribarren; Kevin B Jacobs; John-Olov Jansson; Antti Jula; Mika Kähönen; Sekar Kathiresan; Frank Kee; Kay-Tee Khaw; Mika Kivimäki; Wolfgang Koenig; Aldi T Kraja; Meena Kumari; Kari Kuulasmaa; Johanna Kuusisto; Jaana H Laitinen; Timo A Lakka; Claudia Langenberg; Lenore J Launer; Lars  Lind; Jaana Lindström; Jianjun Liu; Antonio Liuzzi; Marja-Liisa Lokki; Mattias Lorentzon; Pamela A Madden; Patrik K Magnusson; Paolo Manunta; Diana Marek; Winfried März; Irene Mateo Leach; Barbara McKnight; Sarah E Medland; Evelin Mihailov; Lili Milani; Grant W Montgomery; Vincent Mooser; Thomas W Mühleisen; Patricia B Munroe; Arthur W Musk; Narisu Narisu; Gerjan Navis; George Nicholson; Ellen A Nohr; Ken K Ong; Ben A Oostra; Colin N A Palmer; Aarno Palotie; John F Peden; Nancy Pedersen; Annette Peters; Ozren Polasek; Anneli Pouta; Peter P Pramstaller; Inga Prokopenko; Carolin Pütter; Aparna Radhakrishnan; Olli Raitakari; Augusto Rendon; Fernando Rivadeneira; Igor Rudan; Timo E Saaristo; Jennifer G Sambrook; Alan R Sanders; Serena Sanna; Jouko Saramies; Sabine Schipf; Stefan Schreiber; Heribert Schunkert; So-Youn Shin; Stefano Signorini; Juha Sinisalo; Boris Skrobek; Nicole Soranzo; Alena Stan?áková; Klaus Stark; Jonathan C Stephens; Kathleen Stirrups; Ronald P Stolk; Michael Stumvoll; Amy J Swift; Eirini V Theodoraki; Barbara Thorand; David-Alexandre Tregouet; Elena Tremoli; Melanie M Van der Klauw; Joyce B J van Meurs; Sita H Vermeulen; Jorma Viikari; Jarmo Virtamo; Veronique Vitart; Gérard Waeber; Zhaoming Wang; Elisabeth Widén; Sarah H Wild; Gonneke Willemsen; Bernhard R Winkelmann; Jacqueline C M Witteman; Bruce H R Wolffenbuttel; Andrew Wong; Alan F Wright; M Carola Zillikens; Philippe Amouyel; Bernhard O Boehm; Eric Boerwinkle; Dorret I Boomsma; Mark J Caulfield; Stephen J Chanock; L Adrienne Cupples; Daniele Cusi; George V Dedoussis; Jeanette Erdmann; Johan G Eriksson; Paul W Franks; Philippe Froguel; Christian Gieger; Ulf Gyllensten; Anders Hamsten; Tamara B Harris; Christian Hengstenberg; Andrew A Hicks; Aroon Hingorani; Anke Hinney; Albert Hofman; Kees G Hovingh; Kristian Hveem; Thomas Illig; Marjo-Riitta Jarvelin; Karl-Heinz Jöckel; Sirkka M Keinanen-Kiukaanniemi; Lambertus A Kiemeney; Diana Kuh; Markku Laakso; Terho Lehtimäki; Douglas F Levinson; Nicholas G Martin; Andres Metspalu; Andrew D Morris; Markku S Nieminen; Inger Njølstad; Claes Ohlsson; Albertine J Oldehinkel; Willem H Ouwehand; Lyle J Palmer; Brenda Penninx; Chris Power; Michael A Province; Bruce M Psaty; Lu Qi; Rainer Rauramaa; Paul M Ridker; Samuli Ripatti; Veikko Salomaa; Nilesh J Samani; Harold Snieder; Thorkild I A Sørensen; Timothy D Spector; Kari Stefansson; Anke Tönjes; Jaakko Tuomilehto; André G Uitterlinden; Matti Uusitupa; Pim van der Harst; Peter Vollenweider; Henri Wallaschofski; Nicholas J Wareham; Hugh Watkins; H-Erich Wichmann; James Wilson; Goncalo R Abecasis; Themistocles L Assimes; Inês Barroso; Michael Boehnke; Ingrid B Borecki; Panos Deloukas; Caroline S Fox; Timothy Frayling; Leif C Groop; Talin Haritunian; Iris M Heid; David Hunter; Robert C Kaplan; Fredrik Karpe; Miriam F Moffatt; Karen L Mohlke; Jeffrey R O'Connell; Yudi Pawitan; Eric E Schadt; David Schlessinger; Valgerdur Steinthorsdottir; David P Strachan; Unnur Thorsteinsdottir; Cornelia M van Duijn; Peter M Visscher; Anna Maria Di Blasio; Joel N Hirschhorn; Cecilia M Lindgren; Andrew P Morris; David Meyre; André Scherag; Mark I McCarthy; Elizabeth K Speliotes; Kari E North; Ruth J F Loos; Erik Ingelsson

doi:10.1038/ng.2606

Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture

Sonja I Berndt, Stefan Gustafsson, Reedik Mägi, Andrea Ganna, Eleanor Wheeler, Mary F Feitosa, Anne E Justice, Keri L Monda, Damien C Croteau-Chonka, Felix R Day, Tõnu Esko, Tove Fall, Teresa Ferreira, Davide Gentilini, Anne U Jackson, Jian'an Luan, Joshua C Randall, Sailaja Vedantam, Cristen J Willer, Thomas WinklerAndrew R Wood, Tsegaselassie Workalemahu, Yi-Juan Hu, Sang Hong Lee, Liming Liang, Dan-Yu Lin, Josine L Min, Benjamin M Neale, Gudmar Thorleifsson, Jian Yang, Eva Albrecht, Najaf Amin, Jennifer L Bragg-Gresham, Gemma Cadby, Martin den Heijer, Niina Eklund, Krista Fischer, Anuj Goel, Jouke-Jan Hottenga, Jennifer E Huffman, Ivonne Jarick, Åsa Johansson, Toby Johnson, Stavroula Kanoni, Marcus E Kleber, Inke R König, Kati Kristiansson, Zoltán Kutalik, Claudia Lamina, Cecile Lecoeur, Guo Li, Massimo Mangino, Wendy L McArdle, Carolina Medina-Gomez, Martina Müller-Nurasyid, Julius S Ngwa, Ilja M Nolte, Lavinia Paternoster, Sonali Pechlivanis, Markus Perola, Marjolein J Peters, Michael Preuss, Lynda M Rose, Jianxin Shi, Dmitry Shungin, Albert Vernon Smith, Rona J Strawbridge, Ida Surakka, Alexander Teumer, Mieke D Trip, Jonathan Tyrer, Jana V Van Vliet-Ostaptchouk, Liesbeth Vandenput, Lindsay L Waite, Jing Hua Zhao, Devin Absher, Folkert W Asselbergs, Mustafa Atalay, Antony P Attwood, Anthony J Balmforth, Hanneke Basart, John Beilby, Lori L Bonnycastle, Paolo Brambilla, Marcel Bruinenberg, Harry Campbell, Daniel I Chasman, Peter S Chines, Francis S Collins, John M Connell, William O Cookson, Ulf de Faire, Femmie de Vegt, Mariano Dei, Maria Dimitriou, Sarah Edkins, Karol Estrada, David M Evans, Martin Farrall, Marco M Ferrario, Jean Ferrières, Lude Franke, Francesca Frau, Pablo V Gejman, Harald Grallert, Henrik Grönberg, Vilmundur Gudnason, Alistair S Hall, Per Hall, Anna-Liisa Hartikainen, Caroline Hayward, Nancy L Heard-Costa, Andrew C Heath, Johannes Hebebrand, Georg Homuth, Frank B Hu, Sarah E Hunt, Elina Hyppönen, Carlos Iribarren, Kevin B Jacobs, John-Olov Jansson, Antti Jula, Mika Kähönen, Sekar Kathiresan, Frank Kee, Kay-Tee Khaw, Mika Kivimäki, Wolfgang Koenig, Aldi T Kraja, Meena Kumari, Kari Kuulasmaa, Johanna Kuusisto, Jaana H Laitinen, Timo A Lakka, Claudia Langenberg, Lenore J Launer, Lars Lind, Jaana Lindström, Jianjun Liu, Antonio Liuzzi, Marja-Liisa Lokki, Mattias Lorentzon, Pamela A Madden, Patrik K Magnusson, Paolo Manunta, Diana Marek, Winfried März, Irene Mateo Leach, Barbara McKnight, Sarah E Medland, Evelin Mihailov, Lili Milani, Grant W Montgomery, Vincent Mooser, Thomas W Mühleisen, Patricia B Munroe, Arthur W Musk, Narisu Narisu, Gerjan Navis, George Nicholson, Ellen A Nohr, Ken K Ong, Ben A Oostra, Colin N A Palmer, Aarno Palotie, John F Peden, Nancy Pedersen, Annette Peters, Ozren Polasek, Anneli Pouta, Peter P Pramstaller, Inga Prokopenko, Carolin Pütter, Aparna Radhakrishnan, Olli Raitakari, Augusto Rendon, Fernando Rivadeneira, Igor Rudan, Timo E Saaristo, Jennifer G Sambrook, Alan R Sanders, Serena Sanna, Jouko Saramies, Sabine Schipf, Stefan Schreiber, Heribert Schunkert, So-Youn Shin, Stefano Signorini, Juha Sinisalo, Boris Skrobek, Nicole Soranzo, Alena Stan?áková, Klaus Stark, Jonathan C Stephens, Kathleen Stirrups, Ronald P Stolk, Michael Stumvoll, Amy J Swift, Eirini V Theodoraki, Barbara Thorand, David-Alexandre Tregouet, Elena Tremoli, Melanie M Van der Klauw, Joyce B J van Meurs, Sita H Vermeulen, Jorma Viikari, Jarmo Virtamo, Veronique Vitart, Gérard Waeber, Zhaoming Wang, Elisabeth Widén, Sarah H Wild, Gonneke Willemsen, Bernhard R Winkelmann, Jacqueline C M Witteman, Bruce H R Wolffenbuttel, Andrew Wong, Alan F Wright, M Carola Zillikens, Philippe Amouyel, Bernhard O Boehm, Eric Boerwinkle, Dorret I Boomsma, Mark J Caulfield, Stephen J Chanock, L Adrienne Cupples, Daniele Cusi, George V Dedoussis, Jeanette Erdmann, Johan G Eriksson, Paul W Franks, Philippe Froguel, Christian Gieger, Ulf Gyllensten, Anders Hamsten, Tamara B Harris, Christian Hengstenberg, Andrew A Hicks, Aroon Hingorani, Anke Hinney, Albert Hofman, Kees G Hovingh, Kristian Hveem, Thomas Illig, Marjo-Riitta Jarvelin, Karl-Heinz Jöckel, Sirkka M Keinanen-Kiukaanniemi, Lambertus A Kiemeney, Diana Kuh, Markku Laakso, Terho Lehtimäki, Douglas F Levinson, Nicholas G Martin, Andres Metspalu, Andrew D Morris, Markku S Nieminen, Inger Njølstad, Claes Ohlsson, Albertine J Oldehinkel, Willem H Ouwehand, Lyle J Palmer, Brenda Penninx, Chris Power, Michael A Province, Bruce M Psaty, Lu Qi, Rainer Rauramaa, Paul M Ridker, Samuli Ripatti, Veikko Salomaa, Nilesh J Samani, Harold Snieder, Thorkild I A Sørensen, Timothy D Spector, Kari Stefansson, Anke Tönjes, Jaakko Tuomilehto, André G Uitterlinden, Matti Uusitupa, Pim van der Harst, Peter Vollenweider, Henri Wallaschofski, Nicholas J Wareham, Hugh Watkins, H-Erich Wichmann, James Wilson, Goncalo R Abecasis, Themistocles L Assimes, Inês Barroso, Michael Boehnke, Ingrid B Borecki, Panos Deloukas, Caroline S Fox, Timothy Frayling, Leif C Groop, Talin Haritunian, Iris M Heid, David Hunter, Robert C Kaplan, Fredrik Karpe, Miriam F Moffatt, Karen L Mohlke, Jeffrey R O'Connell, Yudi Pawitan, Eric E Schadt, David Schlessinger, Valgerdur Steinthorsdottir, David P Strachan, Unnur Thorsteinsdottir, Cornelia M van Duijn, Peter M Visscher, Anna Maria Di Blasio, Joel N Hirschhorn, Cecilia M Lindgren, Andrew P Morris, David Meyre, André Scherag, Mark I McCarthy, Elizabeth K Speliotes, Kari E North, Ruth J F Loos, Erik Ingelsson

Department of Public Health

369 Citations (Scopus)

Abstract

Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.

Translated title of the contribution	Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
Original language	English
Journal	Nature Genetics
Volume	45
Issue number	5
Pages (from-to)	501-512
Number of pages	12
ISSN	1061-4036
DOIs	https://doi.org/10.1038/ng.2606
Publication status	Published - May 2013

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Berndt, S. I., Gustafsson, S., Mägi, R., Ganna, A., Wheeler, E., Feitosa, M. F., Justice, A. E., Monda, K. L., Croteau-Chonka, D. C., Day, F. R., Esko, T., Fall, T., Ferreira, T., Gentilini, D., Jackson, A. U., Luan, J., Randall, J. C., Vedantam, S., Willer, C. J., ... Ingelsson, E. (2013). Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture. Nature Genetics, 45(5), 501-512. https://doi.org/10.1038/ng.2606

Berndt, SI, Gustafsson, S, Mägi, R, Ganna, A, Wheeler, E, Feitosa, MF, Justice, AE, Monda, KL, Croteau-Chonka, DC, Day, FR, Esko, T, Fall, T, Ferreira, T, Gentilini, D, Jackson, AU, Luan, J, Randall, JC, Vedantam, S, Willer, CJ, Winkler, T, Wood, AR, Workalemahu, T, Hu, Y-J, Lee, SH, Liang, L, Lin, D-Y, Min, JL, Neale, BM, Thorleifsson, G, Yang, J, Albrecht, E, Amin, N, Bragg-Gresham, JL, Cadby, G, den Heijer, M, Eklund, N, Fischer, K, Goel, A, Hottenga, J-J, Huffman, JE, Jarick, I, Johansson, Å, Johnson, T, Kanoni, S, Kleber, ME, König, IR, Kristiansson, K, Kutalik, Z, Lamina, C, Lecoeur, C, Li, G, Mangino, M, McArdle, WL, Medina-Gomez, C, Müller-Nurasyid, M, Ngwa, JS, Nolte, IM, Paternoster, L, Pechlivanis, S, Perola, M, Peters, MJ, Preuss, M, Rose, LM, Shi, J, Shungin, D, Smith, AV, Strawbridge, RJ, Surakka, I, Teumer, A, Trip, MD, Tyrer, J, Van Vliet-Ostaptchouk, JV, Vandenput, L, Waite, LL, Zhao, JH, Absher, D, Asselbergs, FW, Atalay, M, Attwood, AP, Balmforth, AJ, Basart, H, Beilby, J, Bonnycastle, LL, Brambilla, P, Bruinenberg, M, Campbell, H, Chasman, DI, Chines, PS, Collins, FS, Connell, JM, Cookson, WO, de Faire, U, de Vegt, F, Dei, M, Dimitriou, M, Edkins, S, Estrada, K, Evans, DM, Farrall, M, Ferrario, MM, Ferrières, J, Franke, L, Frau, F, Gejman, PV, Grallert, H, Grönberg, H, Gudnason, V, Hall, AS, Hall, P, Hartikainen, A-L, Hayward, C, Heard-Costa, NL, Heath, AC, Hebebrand, J, Homuth, G, Hu, FB, Hunt, SE, Hyppönen, E, Iribarren, C, Jacobs, KB, Jansson, J-O, Jula, A, Kähönen, M, Kathiresan, S, Kee, F, Khaw, K-T, Kivimäki, M, Koenig, W, Kraja, AT, Kumari, M, Kuulasmaa, K, Kuusisto, J, Laitinen, JH, Lakka, TA, Langenberg, C, Launer, LJ, Lind, L, Lindström, J, Liu, J, Liuzzi, A, Lokki, M-L, Lorentzon, M, Madden, PA, Magnusson, PK, Manunta, P, Marek, D, März, W, Mateo Leach, I, McKnight, B, Medland, SE, Mihailov, E, Milani, L, Montgomery, GW, Mooser, V, Mühleisen, TW, Munroe, PB, Musk, AW, Narisu, N, Navis, G, Nicholson, G, Nohr, EA, Ong, KK, Oostra, BA, Palmer, CNA, Palotie, A, Peden, JF, Pedersen, N, Peters, A, Polasek, O, Pouta, A, Pramstaller, PP, Prokopenko, I, Pütter, C, Radhakrishnan, A, Raitakari, O, Rendon, A, Rivadeneira, F, Rudan, I, Saaristo, TE, Sambrook, JG, Sanders, AR, Sanna, S, Saramies, J, Schipf, S, Schreiber, S, Schunkert, H, Shin, S-Y, Signorini, S, Sinisalo, J, Skrobek, B, Soranzo, N, Stan?áková, A, Stark, K, Stephens, JC, Stirrups, K, Stolk, RP, Stumvoll, M, Swift, AJ, Theodoraki, EV, Thorand, B, Tregouet, D-A, Tremoli, E, Van der Klauw, MM, van Meurs, JBJ, Vermeulen, SH, Viikari, J, Virtamo, J, Vitart, V, Waeber, G, Wang, Z, Widén, E, Wild, SH, Willemsen, G, Winkelmann, BR, Witteman, JCM, Wolffenbuttel, BHR, Wong, A, Wright, AF, Zillikens, MC, Amouyel, P, Boehm, BO, Boerwinkle, E, Boomsma, DI, Caulfield, MJ, Chanock, SJ, Cupples, LA, Cusi, D, Dedoussis, GV, Erdmann, J, Eriksson, JG, Franks, PW, Froguel, P, Gieger, C, Gyllensten, U, Hamsten, A, Harris, TB, Hengstenberg, C, Hicks, AA, Hingorani, A, Hinney, A, Hofman, A, Hovingh, KG, Hveem, K, Illig, T, Jarvelin, M-R, Jöckel, K-H, Keinanen-Kiukaanniemi, SM, Kiemeney, LA, Kuh, D, Laakso, M, Lehtimäki, T, Levinson, DF, Martin, NG, Metspalu, A, Morris, AD, Nieminen, MS, Njølstad, I, Ohlsson, C, Oldehinkel, AJ, Ouwehand, WH, Palmer, LJ, Penninx, B, Power, C, Province, MA, Psaty, BM, Qi, L, Rauramaa, R, Ridker, PM, Ripatti, S, Salomaa, V, Samani, NJ, Snieder, H, Sørensen, TIA, Spector, TD, Stefansson, K, Tönjes, A, Tuomilehto, J, Uitterlinden, AG, Uusitupa, M, van der Harst, P, Vollenweider, P, Wallaschofski, H, Wareham, NJ, Watkins, H, Wichmann, H-E, Wilson, J, Abecasis, GR, Assimes, TL, Barroso, I, Boehnke, M, Borecki, IB, Deloukas, P, Fox, CS, Frayling, T, Groop, LC, Haritunian, T, Heid, IM, Hunter, D, Kaplan, RC, Karpe, F, Moffatt, MF, Mohlke, KL, O'Connell, JR, Pawitan, Y, Schadt, EE, Schlessinger, D, Steinthorsdottir, V, Strachan, DP, Thorsteinsdottir, U, van Duijn, CM, Visscher, PM, Di Blasio, AM, Hirschhorn, JN, Lindgren, CM, Morris, AP, Meyre, D, Scherag, A, McCarthy, MI, Speliotes, EK, North, KE, Loos, RJF & Ingelsson, E 2013, 'Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture', Nature Genetics, vol. 45, no. 5, pp. 501-512. https://doi.org/10.1038/ng.2606

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title = "Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture",

abstract = "Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.",

author = "Berndt, {Sonja I} and Stefan Gustafsson and Reedik M{\"a}gi and Andrea Ganna and Eleanor Wheeler and Feitosa, {Mary F} and Justice, {Anne E} and Monda, {Keri L} and Croteau-Chonka, {Damien C} and Day, {Felix R} and T{\~o}nu Esko and Tove Fall and Teresa Ferreira and Davide Gentilini and Jackson, {Anne U} and Jian'an Luan and Randall, {Joshua C} and Sailaja Vedantam and Willer, {Cristen J} and Thomas Winkler and Wood, {Andrew R} and Tsegaselassie Workalemahu and Yi-Juan Hu and Lee, {Sang Hong} and Liming Liang and Dan-Yu Lin and Min, {Josine L} and Neale, {Benjamin M} and Gudmar Thorleifsson and Jian Yang and Eva Albrecht and Najaf Amin and Bragg-Gresham, {Jennifer L} and Gemma Cadby and {den Heijer}, Martin and Niina Eklund and Krista Fischer and Anuj Goel and Jouke-Jan Hottenga and Huffman, {Jennifer E} and Ivonne Jarick and {\AA}sa Johansson and Toby Johnson and Stavroula Kanoni and Kleber, {Marcus E} and K{\"o}nig, {Inke R} and Kati Kristiansson and Zolt{\'a}n Kutalik and Claudia Lamina and Cecile Lecoeur and Guo Li and Massimo Mangino and McArdle, {Wendy L} and Carolina Medina-Gomez and Martina M{\"u}ller-Nurasyid and Ngwa, {Julius S} and Nolte, {Ilja M} and Lavinia Paternoster and Sonali Pechlivanis and Markus Perola and Peters, {Marjolein J} and Michael Preuss and Rose, {Lynda M} and Jianxin Shi and Dmitry Shungin and Smith, {Albert Vernon} and Strawbridge, {Rona J} and Ida Surakka and Alexander Teumer and Trip, {Mieke D} and Jonathan Tyrer and {Van Vliet-Ostaptchouk}, {Jana V} and Liesbeth Vandenput and Waite, {Lindsay L} and Zhao, {Jing Hua} and Devin Absher and Asselbergs, {Folkert W} and Mustafa Atalay and Attwood, {Antony P} and Balmforth, {Anthony J} and Hanneke Basart and John Beilby and Bonnycastle, {Lori L} and Paolo Brambilla and Marcel Bruinenberg and Harry Campbell and Chasman, {Daniel I} and Chines, {Peter S} and Collins, {Francis S} and Connell, {John M} and Cookson, {William O} and {de Faire}, Ulf and {de Vegt}, Femmie and Mariano Dei and Maria Dimitriou and Sarah Edkins and Karol Estrada and Evans, {David M} and Martin Farrall and Ferrario, {Marco M} and Jean Ferri{\`e}res and Lude Franke and Francesca Frau and Gejman, {Pablo V} and Harald Grallert and Henrik Gr{\"o}nberg and Vilmundur Gudnason and Hall, {Alistair S} and Per Hall and Anna-Liisa Hartikainen and Caroline Hayward and Heard-Costa, {Nancy L} and Heath, {Andrew C} and Johannes Hebebrand and Georg Homuth and Hu, {Frank B} and Hunt, {Sarah E} and Elina Hypp{\"o}nen and Carlos Iribarren and Jacobs, {Kevin B} and John-Olov Jansson and Antti Jula and Mika K{\"a}h{\"o}nen and Sekar Kathiresan and Frank Kee and Kay-Tee Khaw and Mika Kivim{\"a}ki and Wolfgang Koenig and Kraja, {Aldi T} and Meena Kumari and Kari Kuulasmaa and Johanna Kuusisto and Laitinen, {Jaana H} and Lakka, {Timo A} and Claudia Langenberg and Launer, {Lenore J} and Lars Lind and Jaana Lindstr{\"o}m and Jianjun Liu and Antonio Liuzzi and Marja-Liisa Lokki and Mattias Lorentzon and Madden, {Pamela A} and Magnusson, {Patrik K} and Paolo Manunta and Diana Marek and Winfried M{\"a}rz and {Mateo Leach}, Irene and Barbara McKnight and Medland, {Sarah E} and Evelin Mihailov and Lili Milani and Montgomery, {Grant W} and Vincent Mooser and M{\"u}hleisen, {Thomas W} and Munroe, {Patricia B} and Musk, {Arthur W} and Narisu Narisu and Gerjan Navis and George Nicholson and Nohr, {Ellen A} and Ong, {Ken K} and Oostra, {Ben A} and Palmer, {Colin N A} and Aarno Palotie and Peden, {John F} and Nancy Pedersen and Annette Peters and Ozren Polasek and Anneli Pouta and Pramstaller, {Peter P} and Inga Prokopenko and Carolin P{\"u}tter and Aparna Radhakrishnan and Olli Raitakari and Augusto Rendon and Fernando Rivadeneira and Igor Rudan and Saaristo, {Timo E} and Sambrook, {Jennifer G} and Sanders, {Alan R} and Serena Sanna and Jouko Saramies and Sabine Schipf and Stefan Schreiber and Heribert Schunkert and So-Youn Shin and Stefano Signorini and Juha Sinisalo and Boris Skrobek and Nicole Soranzo and Alena Stan?{\'a}kov{\'a} and Klaus Stark and Stephens, {Jonathan C} and Kathleen Stirrups and Stolk, {Ronald P} and Michael Stumvoll and Swift, {Amy J} and Theodoraki, {Eirini V} and Barbara Thorand and David-Alexandre Tregouet and Elena Tremoli and {Van der Klauw}, {Melanie M} and {van Meurs}, {Joyce B J} and Vermeulen, {Sita H} and Jorma Viikari and Jarmo Virtamo and Veronique Vitart and G{\'e}rard Waeber and Zhaoming Wang and Elisabeth Wid{\'e}n and Wild, {Sarah H} and Gonneke Willemsen and Winkelmann, {Bernhard R} and Witteman, {Jacqueline C M} and Wolffenbuttel, {Bruce H R} and Andrew Wong and Wright, {Alan F} and Zillikens, {M Carola} and Philippe Amouyel and Boehm, {Bernhard O} and Eric Boerwinkle and Boomsma, {Dorret I} and Caulfield, {Mark J} and Chanock, {Stephen J} and Cupples, {L Adrienne} and Daniele Cusi and Dedoussis, {George V} and Jeanette Erdmann and Eriksson, {Johan G} and Franks, {Paul W} and Philippe Froguel and Christian Gieger and Ulf Gyllensten and Anders Hamsten and Harris, {Tamara B} and Christian Hengstenberg and Hicks, {Andrew A} and Aroon Hingorani and Anke Hinney and Albert Hofman and Hovingh, {Kees G} and Kristian Hveem and Thomas Illig and Marjo-Riitta Jarvelin and Karl-Heinz J{\"o}ckel and Keinanen-Kiukaanniemi, {Sirkka M} and Kiemeney, {Lambertus A} and Diana Kuh and Markku Laakso and Terho Lehtim{\"a}ki and Levinson, {Douglas F} and Martin, {Nicholas G} and Andres Metspalu and Morris, {Andrew D} and Nieminen, {Markku S} and Inger Nj{\o}lstad and Claes Ohlsson and Oldehinkel, {Albertine J} and Ouwehand, {Willem H} and Palmer, {Lyle J} and Brenda Penninx and Chris Power and Province, {Michael A} and Psaty, {Bruce M} and Lu Qi and Rainer Rauramaa and Ridker, {Paul M} and Samuli Ripatti and Veikko Salomaa and Samani, {Nilesh J} and Harold Snieder and S{\o}rensen, {Thorkild I A} and Spector, {Timothy D} and Kari Stefansson and Anke T{\"o}njes and Jaakko Tuomilehto and Uitterlinden, {Andr{\'e} G} and Matti Uusitupa and {van der Harst}, Pim and Peter Vollenweider and Henri Wallaschofski and Wareham, {Nicholas J} and Hugh Watkins and H-Erich Wichmann and James Wilson and Abecasis, {Goncalo R} and Assimes, {Themistocles L} and In{\^e}s Barroso and Michael Boehnke and Borecki, {Ingrid B} and Panos Deloukas and Fox, {Caroline S} and Timothy Frayling and Groop, {Leif C} and Talin Haritunian and Heid, {Iris M} and David Hunter and Kaplan, {Robert C} and Fredrik Karpe and Moffatt, {Miriam F} and Mohlke, {Karen L} and O'Connell, {Jeffrey R} and Yudi Pawitan and Schadt, {Eric E} and David Schlessinger and Valgerdur Steinthorsdottir and Strachan, {David P} and Unnur Thorsteinsdottir and {van Duijn}, {Cornelia M} and Visscher, {Peter M} and {Di Blasio}, {Anna Maria} and Hirschhorn, {Joel N} and Lindgren, {Cecilia M} and Morris, {Andrew P} and David Meyre and Andr{\'e} Scherag and McCarthy, {Mark I} and Speliotes, {Elizabeth K} and North, {Kari E} and Loos, {Ruth J F} and Erik Ingelsson",

year = "2013",

month = may,

doi = "10.1038/ng.2606",

language = "English",

volume = "45",

pages = "501--512",

journal = "Nature: New biology",

issn = "1061-4036",

publisher = "nature publishing group",

number = "5",

}

TY - JOUR

T1 - Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture

AU - Berndt, Sonja I

AU - Gustafsson, Stefan

AU - Mägi, Reedik

AU - Ganna, Andrea

AU - Wheeler, Eleanor

AU - Feitosa, Mary F

AU - Justice, Anne E

AU - Monda, Keri L

AU - Croteau-Chonka, Damien C

AU - Day, Felix R

AU - Esko, Tõnu

AU - Fall, Tove

AU - Ferreira, Teresa

AU - Gentilini, Davide

AU - Jackson, Anne U

AU - Luan, Jian'an

AU - Randall, Joshua C

AU - Vedantam, Sailaja

AU - Willer, Cristen J

AU - Winkler, Thomas

AU - Wood, Andrew R

AU - Workalemahu, Tsegaselassie

AU - Hu, Yi-Juan

AU - Lee, Sang Hong

AU - Liang, Liming

AU - Lin, Dan-Yu

AU - Min, Josine L

AU - Neale, Benjamin M

AU - Thorleifsson, Gudmar

AU - Yang, Jian

AU - Albrecht, Eva

AU - Amin, Najaf

AU - Bragg-Gresham, Jennifer L

AU - Cadby, Gemma

AU - den Heijer, Martin

AU - Eklund, Niina

AU - Fischer, Krista

AU - Goel, Anuj

AU - Hottenga, Jouke-Jan

AU - Huffman, Jennifer E

AU - Jarick, Ivonne

AU - Johansson, Åsa

AU - Johnson, Toby

AU - Kanoni, Stavroula

AU - Kleber, Marcus E

AU - König, Inke R

AU - Kristiansson, Kati

AU - Kutalik, Zoltán

AU - Lamina, Claudia

AU - Lecoeur, Cecile

AU - Li, Guo

AU - Mangino, Massimo

AU - McArdle, Wendy L

AU - Medina-Gomez, Carolina

AU - Müller-Nurasyid, Martina

AU - Ngwa, Julius S

AU - Nolte, Ilja M

AU - Paternoster, Lavinia

AU - Pechlivanis, Sonali

AU - Perola, Markus

AU - Peters, Marjolein J

AU - Preuss, Michael

AU - Rose, Lynda M

AU - Shi, Jianxin

AU - Shungin, Dmitry

AU - Smith, Albert Vernon

AU - Strawbridge, Rona J

AU - Surakka, Ida

AU - Teumer, Alexander

AU - Trip, Mieke D

AU - Tyrer, Jonathan

AU - Van Vliet-Ostaptchouk, Jana V

AU - Vandenput, Liesbeth

AU - Waite, Lindsay L

AU - Zhao, Jing Hua

AU - Absher, Devin

AU - Asselbergs, Folkert W

AU - Atalay, Mustafa

AU - Attwood, Antony P

AU - Balmforth, Anthony J

AU - Basart, Hanneke

AU - Beilby, John

AU - Bonnycastle, Lori L

AU - Brambilla, Paolo

AU - Bruinenberg, Marcel

AU - Campbell, Harry

AU - Chasman, Daniel I

AU - Chines, Peter S

AU - Collins, Francis S

AU - Connell, John M

AU - Cookson, William O

AU - de Faire, Ulf

AU - de Vegt, Femmie

AU - Dei, Mariano

AU - Dimitriou, Maria

AU - Edkins, Sarah

AU - Estrada, Karol

AU - Evans, David M

AU - Farrall, Martin

AU - Ferrario, Marco M

AU - Ferrières, Jean

AU - Franke, Lude

AU - Frau, Francesca

AU - Gejman, Pablo V

AU - Grallert, Harald

AU - Grönberg, Henrik

AU - Gudnason, Vilmundur

AU - Hall, Alistair S

AU - Hall, Per

AU - Hartikainen, Anna-Liisa

AU - Hayward, Caroline

AU - Heard-Costa, Nancy L

AU - Heath, Andrew C

AU - Hebebrand, Johannes

AU - Homuth, Georg

AU - Hu, Frank B

AU - Hunt, Sarah E

AU - Hyppönen, Elina

AU - Iribarren, Carlos

AU - Jacobs, Kevin B

AU - Jansson, John-Olov

AU - Jula, Antti

AU - Kähönen, Mika

AU - Kathiresan, Sekar

AU - Kee, Frank

AU - Khaw, Kay-Tee

AU - Kivimäki, Mika

AU - Koenig, Wolfgang

AU - Kraja, Aldi T

AU - Kumari, Meena

AU - Kuulasmaa, Kari

AU - Kuusisto, Johanna

AU - Laitinen, Jaana H

AU - Lakka, Timo A

AU - Langenberg, Claudia

AU - Launer, Lenore J

AU - Lind, Lars

AU - Lindström, Jaana

AU - Liu, Jianjun

AU - Liuzzi, Antonio

AU - Lokki, Marja-Liisa

AU - Lorentzon, Mattias

AU - Madden, Pamela A

AU - Magnusson, Patrik K

AU - Manunta, Paolo

AU - Marek, Diana

AU - März, Winfried

AU - Mateo Leach, Irene

AU - McKnight, Barbara

AU - Medland, Sarah E

AU - Mihailov, Evelin

AU - Milani, Lili

AU - Montgomery, Grant W

AU - Mooser, Vincent

AU - Mühleisen, Thomas W

AU - Munroe, Patricia B

AU - Musk, Arthur W

AU - Narisu, Narisu

AU - Navis, Gerjan

AU - Nicholson, George

AU - Nohr, Ellen A

AU - Ong, Ken K

AU - Oostra, Ben A

AU - Palmer, Colin N A

AU - Palotie, Aarno

AU - Peden, John F

AU - Pedersen, Nancy

AU - Peters, Annette

AU - Polasek, Ozren

AU - Pouta, Anneli

AU - Pramstaller, Peter P

AU - Prokopenko, Inga

AU - Pütter, Carolin

AU - Radhakrishnan, Aparna

AU - Raitakari, Olli

AU - Rendon, Augusto

AU - Rivadeneira, Fernando

AU - Rudan, Igor

AU - Saaristo, Timo E

AU - Sambrook, Jennifer G

AU - Sanders, Alan R

AU - Sanna, Serena

AU - Saramies, Jouko

AU - Schipf, Sabine

AU - Schreiber, Stefan

AU - Schunkert, Heribert

AU - Shin, So-Youn

AU - Signorini, Stefano

AU - Sinisalo, Juha

AU - Skrobek, Boris

AU - Soranzo, Nicole

AU - Stan?áková, Alena

AU - Stark, Klaus

AU - Stephens, Jonathan C

AU - Stirrups, Kathleen

AU - Stolk, Ronald P

AU - Stumvoll, Michael

AU - Swift, Amy J

AU - Theodoraki, Eirini V

AU - Thorand, Barbara

AU - Tregouet, David-Alexandre

AU - Tremoli, Elena

AU - Van der Klauw, Melanie M

AU - van Meurs, Joyce B J

AU - Vermeulen, Sita H

AU - Viikari, Jorma

AU - Virtamo, Jarmo

AU - Vitart, Veronique

AU - Waeber, Gérard

AU - Wang, Zhaoming

AU - Widén, Elisabeth

AU - Wild, Sarah H

AU - Willemsen, Gonneke

AU - Winkelmann, Bernhard R

AU - Witteman, Jacqueline C M

AU - Wolffenbuttel, Bruce H R

AU - Wong, Andrew

AU - Wright, Alan F

AU - Zillikens, M Carola

AU - Amouyel, Philippe

AU - Boehm, Bernhard O

AU - Boerwinkle, Eric

AU - Boomsma, Dorret I

AU - Caulfield, Mark J

AU - Chanock, Stephen J

AU - Cupples, L Adrienne

AU - Cusi, Daniele

AU - Dedoussis, George V

AU - Erdmann, Jeanette

AU - Eriksson, Johan G

AU - Franks, Paul W

AU - Froguel, Philippe

AU - Gieger, Christian

AU - Gyllensten, Ulf

AU - Hamsten, Anders

AU - Harris, Tamara B

AU - Hengstenberg, Christian

AU - Hicks, Andrew A

AU - Hingorani, Aroon

AU - Hinney, Anke

AU - Hofman, Albert

AU - Hovingh, Kees G

AU - Hveem, Kristian

AU - Illig, Thomas

AU - Jarvelin, Marjo-Riitta

AU - Jöckel, Karl-Heinz

AU - Keinanen-Kiukaanniemi, Sirkka M

AU - Kiemeney, Lambertus A

AU - Kuh, Diana

AU - Laakso, Markku

AU - Lehtimäki, Terho

AU - Levinson, Douglas F

AU - Martin, Nicholas G

AU - Metspalu, Andres

AU - Morris, Andrew D

AU - Nieminen, Markku S

AU - Njølstad, Inger

AU - Ohlsson, Claes

AU - Oldehinkel, Albertine J

AU - Ouwehand, Willem H

AU - Palmer, Lyle J

AU - Penninx, Brenda

AU - Power, Chris

AU - Province, Michael A

AU - Psaty, Bruce M

AU - Qi, Lu

AU - Rauramaa, Rainer

AU - Ridker, Paul M

AU - Ripatti, Samuli

AU - Salomaa, Veikko

AU - Samani, Nilesh J

AU - Snieder, Harold

AU - Sørensen, Thorkild I A

AU - Spector, Timothy D

AU - Stefansson, Kari

AU - Tönjes, Anke

AU - Tuomilehto, Jaakko

AU - Uitterlinden, André G

AU - Uusitupa, Matti

AU - van der Harst, Pim

AU - Vollenweider, Peter

AU - Wallaschofski, Henri

AU - Wareham, Nicholas J

AU - Watkins, Hugh

AU - Wichmann, H-Erich

AU - Wilson, James

AU - Abecasis, Goncalo R

AU - Assimes, Themistocles L

AU - Barroso, Inês

AU - Boehnke, Michael

AU - Borecki, Ingrid B

AU - Deloukas, Panos

AU - Fox, Caroline S

AU - Frayling, Timothy

AU - Groop, Leif C

AU - Haritunian, Talin

AU - Heid, Iris M

AU - Hunter, David

AU - Kaplan, Robert C

AU - Karpe, Fredrik

AU - Moffatt, Miriam F

AU - Mohlke, Karen L

AU - O'Connell, Jeffrey R

AU - Pawitan, Yudi

AU - Schadt, Eric E

AU - Schlessinger, David

AU - Steinthorsdottir, Valgerdur

AU - Strachan, David P

AU - Thorsteinsdottir, Unnur

AU - van Duijn, Cornelia M

AU - Visscher, Peter M

AU - Di Blasio, Anna Maria

AU - Hirschhorn, Joel N

AU - Lindgren, Cecilia M

AU - Morris, Andrew P

AU - Meyre, David

AU - Scherag, André

AU - McCarthy, Mark I

AU - Speliotes, Elizabeth K

AU - North, Kari E

AU - Loos, Ruth J F

AU - Ingelsson, Erik

PY - 2013/5

Y1 - 2013/5

N2 - Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.

AB - Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.

U2 - 10.1038/ng.2606

DO - 10.1038/ng.2606

M3 - Journal article

C2 - 23563607

SN - 1061-4036

VL - 45

SP - 501

EP - 512

JO - Nature: New biology

JF - Nature: New biology

IS - 5

ER -

Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture

Abstract

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