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Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
Authors :
Berndt, Sonja I. Gustafsson, Stefan Maegi, Reedik Ganna, Andrea Wheeler, Eleanor Feitosa, Mary F. Justice, Anne E. Monda, Keri L. Croteau-Chonka, Damien C. Day, Felix R. Esko, Tonu Fall, Tove Ferreira, Teresa Gentilini, Davide Jackson, Anne U. Luan, Jian'an Randall, Joshua C. Vedantam, Sailaja Willer, Cristen J. Winkler, Thomas W. Wood, Andrew R. Workalemahu, Tsegaselassie Hu, Yi-Juan Lee, Sang Hong Liang, Liming Lin, Dan-Yu Min, Josine L. Neale, Benjamin M. Thorleifsson, Gudmar Yang, Jian Albrecht, Eva Amin, Najaf Bragg-Gresham, Jennifer L. Cadby, Gemma den Heijer, Martin Eklund, Niina Fischer, Krista Goel, Anuj Hottenga, Jouke-Jan Huffman, Jennifer E. Jarick, Ivonne Johansson, Åsa Johnson, Toby Kanoni, Stavroula Kleber, Marcus E. Koenig, Inke R. Kristiansson, Kati Kutalik, Zoltn Lamina, Claudia Lecoeur, Cecile Li, Guo Mangino, Massimo McArdle, Wendy L. Medina-Gomez, Carolina Mueller-Nurasyid, Martina Ngwa, Julius S. Nolte, Ilja M. Paternoster, Lavinia Pechlivanis, Sonali Perola, Markus Peters, Marjolein J. Preuss, Michael Rose, Lynda M. Shi, Jianxin Shungin, Dmitry Smith, Albert Vernon Strawbridge, Rona J. Surakka, Ida Teumer, Alexander Trip, Mieke D. Tyrer, Jonathan Van Vliet-Ostaptchouk, Jana V. Vandenput, Liesbeth Waite, Lindsay L. Zhao, Jing Hua Absher, Devin Asselbergs, Folkert W. Atalay, Mustafa Attwood, Antony P. Balmforth, Anthony J. Basart, Hanneke Beilby, John Bonnycastle, Lori L. Brambilla, Paolo Bruinenberg, Marcel Campbell, Harry Chasman, Daniel I. Chines, Peter S. Collins, Francis S. Connell, John M. Cookson, William O. de Faire, Ulf de Vegt, Femmie Dei, Mariano Dimitriou, Maria Edkins, Sarah Estrada, Karol Evans, David M. Farrall, Martin Ferrario, Marco M. Ferrieres, Jean Franke, Lude Frau, Francesca Gejman, Pablo V. Grallert, Harald Groenberg, Henrik Gudnason, Vilmundur Hall, Alistair S. Hall, Per Hartikainen, Anna-Liisa Hayward, Caroline Heard-Costa, Nancy L. Heath, Andrew C. Hebebrand, Johannes Homuth, Georg Hu, Frank B. Hunt, Sarah E. Hyppoenen, Elina Iribarren, Carlos Jacobs, Kevin B. Jansson, John-Olov Jula, Antti Kahonen, Mika Kathiresan, Sekar Kee, Frank Khaw, Kay-Tee Kivimaki, Mika Koenig, Wolfgang Kraja, Aldi T. Kumari, Meena Kuulasmaa, Kari Kuusisto, Johanna Laitinen, Jaana H. Lakka, Timo A. Langenberg, Claudia Launer, Lenore J. Lind, Lars Lindström, Jaana Liu, Jianjun Liuzzi, Antonio Lokki, Marja-Liisa Lorentzon, Mattias Madden, Pamela A. Magnusson, Patrik K. Manunta, Paolo Marek, Diana März, Winfried Leach, Irene Mateo McKnight, Barbara Medland, Sarah E. Mihailov, Evelin Milani, Lili Montgomery, Grant W. Mooser, Vincent Muehleisen, Thomas W. Munroe, Patricia B. Musk, Arthur W. Narisu, Narisu Navis, Gerjan Nicholson, George Nohr, Ellen A. Ong, Ken K. Oostra, Ben A. Palmer, Colin N. A. Palotie, Aarno Peden, John F. Pedersen, Nancy Peters, Annette Polasek, Ozren Pouta, Anneli Pramstaller, Peter P. Prokopenko, Inga Puetter, Carolin Radhakrishnan, Aparna Raitakari, Olli Rendon, Augusto Rivadeneira, Fernando Rudan, Igor Saaristo, Timo E. Sambrook, Jennifer G. Sanders, Alan R. Sanna, Serena Saramies, Jouko Schipf, Sabine Schreiber, Stefan Schunkert, Heribert Shin, So-Youn Signorini, Stefano Sinisalo, Juha Skrobek, Boris Soranzo, Nicole Stancakova, Alena Stark, Klaus Stephens, Jonathan C. Stirrups, Kathleen Stolk, Ronald P. Stumvoll, Michael Swift, Amy J. Theodoraki, Eirini V. Thorand, Barbara Tregouet, David-Alexandre Tremoli, Elena Van der Klauw, Melanie M. van Meurs, Joyce B. J. Vermeulen, Sita H. Viikari, Jorma Virtamo, Jarmo Vitart, Veronique Waeber, Gerard Wang, Zhaoming Widen, Elisabeth Wild, Sarah H. Willemsen, Gonneke Winkelmann, Bernhard R. Witteman, Jacqueline C. M. Wolffenbuttel, Bruce H. R. Wong, Andrew Wright, Alan F. Zillikens, M. Carola Amouyel, Philippe Boehm, Bernhard O. Boerwinkle, Eric Boomsma, Dorret I. Caulfield, Mark J. Chanock, Stephen J. Cupples, L. Adrienne Cusi, Daniele Dedoussis, George V. Erdmann, Jeanette Eriksson, Johan G. Franks, Paul W. Froguel, Philippe Gieger, Christian Gyllensten, Ulf Hamsten, Anders Harris, Tamara B. Hengstenberg, Christian Hicks, Andrew A. Hingorani, Aroon Hinney, Anke Hofman, Albert Hovingh, Kees G. Hveem, Kristian Illig, Thomas Jarvelin, Marjo-Riitta Joeckel, Karl-Heinz Keinanen-Kiukaanniemi, Sirkka M. Kiemeney, Lambertus A. Kuh, Diana Laakso, Markku Lehtimaki, Terho Levinson, Douglas F. Martin, Nicholas G. Metspalu, Andres Morris, Andrew D. Nieminen, Markku S. Njolstad, Inger Ohlsson, Claes Oldehinkel, Albertine J. Ouwehand, Willem H. Palmer, Lyle J. Penninx, Brenda Power, Chris Province, Michael A. Psaty, Bruce M. Qi, Lu Rauramaa, Rainer Ridker, Paul M. Ripatti, Samuli Salomaa, Veikko Samani, Nilesh J. Snieder, Harold Sorensen, Thorkild I. A. Spector, Timothy D. Stefansson, Kari Tonjes, Anke Tuomilehto, Jaakko Uitterlinden, Andre G. Uusitupa, Matti van der Harst, Pim Vollenweider, Peter Wallaschofski, Henri Wareham, Nicholas J. Watkins, Hugh Wichmann, H-Erich Wilson, James F. Abecasis, Goncalo R. Assimes, Themistocles L. Barroso, Ines Boehnke, Michael Borecki, Ingrid B. Deloukas, Panos Fox, Caroline S. Frayling, Timothy Groop, Leif C. Haritunian, Talin Heid, Iris M. Hunter, David Kaplan, Robert C. Karpe, Fredrik Moffatt, Miriam F. Mohlke, Karen L. O'Connell, Jeffrey R. Pawitan, Yudi Schadt, Eric E. Schlessinger, David Steinthorsdottir, Valgerdur Strachan, David P. Thorsteinsdottir, Unnur van Duijn, Cornelia M. Visscher, Peter M. Di Blasio, Anna Maria Hirschhorn, Joel N. Lindgren, Cecilia M. Morris, Andrew P. Meyre, David Scherag, Andr McCarthy, Mark I. Speliotes, Elizabeth K. North, Kari E. Loos, Ruth J. F. Ingelsson, Erik Berndt, Sonja I. Gustafsson, Stefan Maegi, Reedik Ganna, Andrea Wheeler, Eleanor Feitosa, Mary F. Justice, Anne E. Monda, Keri L. Croteau-Chonka, Damien C. Day, Felix R. Esko, Tonu Fall, Tove Ferreira, Teresa Gentilini, Davide Jackson, Anne U. Luan, Jian'an Randall, Joshua C. Vedantam, Sailaja Willer, Cristen J. Winkler, Thomas W. Wood, Andrew R. Workalemahu, Tsegaselassie Hu, Yi-Juan Lee, Sang Hong Liang, Liming Lin, Dan-Yu Min, Josine L. Neale, Benjamin M. Thorleifsson, Gudmar Yang, Jian Albrecht, Eva Amin, Najaf Bragg-Gresham, Jennifer L. Cadby, Gemma den Heijer, Martin Eklund, Niina Fischer, Krista Goel, Anuj Hottenga, Jouke-Jan Huffman, Jennifer E. Jarick, Ivonne Johansson, Åsa Johnson, Toby Kanoni, Stavroula Kleber, Marcus E. Koenig, Inke R. Kristiansson, Kati Kutalik, Zoltn Lamina, Claudia Lecoeur, Cecile Li, Guo Mangino, Massimo McArdle, Wendy L. Medina-Gomez, Carolina Mueller-Nurasyid, Martina Ngwa, Julius S. Nolte, Ilja M. Paternoster, Lavinia Pechlivanis, Sonali Perola, Markus Peters, Marjolein J. Preuss, Michael Rose, Lynda M. Shi, Jianxin Shungin, Dmitry Smith, Albert Vernon Strawbridge, Rona J. Surakka, Ida Teumer, Alexander Trip, Mieke D. Tyrer, Jonathan Van Vliet-Ostaptchouk, Jana V. Vandenput, Liesbeth Waite, Lindsay L. Zhao, Jing Hua Absher, Devin Asselbergs, Folkert W. Atalay, Mustafa Attwood, Antony P. Balmforth, Anthony J. Basart, Hanneke Beilby, John Bonnycastle, Lori L. Brambilla, Paolo Bruinenberg, Marcel Campbell, Harry Chasman, Daniel I. Chines, Peter S. Collins, Francis S. Connell, John M. Cookson, William O. de Faire, Ulf de Vegt, Femmie Dei, Mariano Dimitriou, Maria Edkins, Sarah Estrada, Karol Evans, David M. Farrall, Martin Ferrario, Marco M. Ferrieres, Jean Franke, Lude Frau, Francesca Gejman, Pablo V. Grallert, Harald Groenberg, Henrik Gudnason, Vilmundur Hall, Alistair S. Hall, Per Hartikainen, Anna-Liisa Hayward, Caroline Heard-Costa, Nancy L. Heath, Andrew C. Hebebrand, Johannes Homuth, Georg Hu, Frank B. Hunt, Sarah E. Hyppoenen, Elina Iribarren, Carlos Jacobs, Kevin B. Jansson, John-Olov Jula, Antti Kahonen, Mika Kathiresan, Sekar Kee, Frank Khaw, Kay-Tee Kivimaki, Mika Koenig, Wolfgang Kraja, Aldi T. Kumari, Meena Kuulasmaa, Kari Kuusisto, Johanna Laitinen, Jaana H. Lakka, Timo A. Langenberg, Claudia Launer, Lenore J. Lind, Lars Lindström, Jaana Liu, Jianjun Liuzzi, Antonio Lokki, Marja-Liisa Lorentzon, Mattias Madden, Pamela A. Magnusson, Patrik K. Manunta, Paolo Marek, Diana März, Winfried Leach, Irene Mateo McKnight, Barbara Medland, Sarah E. Mihailov, Evelin Milani, Lili Montgomery, Grant W. Mooser, Vincent Muehleisen, Thomas W. Munroe, Patricia B. Musk, Arthur W. Narisu, Narisu Navis, Gerjan Nicholson, George Nohr, Ellen A. Ong, Ken K. Oostra, Ben A. Palmer, Colin N. A. Palotie, Aarno Peden, John F. Pedersen, Nancy Peters, Annette Polasek, Ozren Pouta, Anneli Pramstaller, Peter P. Prokopenko, Inga Puetter, Carolin Radhakrishnan, Aparna Raitakari, Olli Rendon, Augusto Rivadeneira, Fernando Rudan, Igor Saaristo, Timo E. Sambrook, Jennifer G. Sanders, Alan R. Sanna, Serena Saramies, Jouko Schipf, Sabine Schreiber, Stefan Schunkert, Heribert Shin, So-Youn Signorini, Stefano Sinisalo, Juha Skrobek, Boris Soranzo, Nicole Stancakova, Alena Stark, Klaus Stephens, Jonathan C. Stirrups, Kathleen Stolk, Ronald P. Stumvoll, Michael Swift, Amy J. Theodoraki, Eirini V. Thorand, Barbara Tregouet, David-Alexandre Tremoli, Elena Van der Klauw, Melanie M. van Meurs, Joyce B. J. Vermeulen, Sita H. Viikari, Jorma Virtamo, Jarmo Vitart, Veronique Waeber, Gerard Wang, Zhaoming Widen, Elisabeth Wild, Sarah H. Willemsen, Gonneke Winkelmann, Bernhard R. Witteman, Jacqueline C. M. Wolffenbuttel, Bruce H. R. Wong, Andrew Wright, Alan F. Zillikens, M. Carola Amouyel, Philippe Boehm, Bernhard O. Boerwinkle, Eric Boomsma, Dorret I. Caulfield, Mark J. Chanock, Stephen J. Cupples, L. Adrienne Cusi, Daniele Dedoussis, George V. Erdmann, Jeanette Eriksson, Johan G. Franks, Paul W. Froguel, Philippe Gieger, Christian Gyllensten, Ulf Hamsten, Anders Harris, Tamara B. Hengstenberg, Christian Hicks, Andrew A. Hingorani, Aroon Hinney, Anke Hofman, Albert Hovingh, Kees G. Hveem, Kristian Illig, Thomas Jarvelin, Marjo-Riitta Joeckel, Karl-Heinz Keinanen-Kiukaanniemi, Sirkka M. Kiemeney, Lambertus A. Kuh, Diana Laakso, Markku Lehtimaki, Terho Levinson, Douglas F. Martin, Nicholas G. Metspalu, Andres Morris, Andrew D. Nieminen, Markku S. Njolstad, Inger Ohlsson, Claes Oldehinkel, Albertine J. Ouwehand, Willem H. Palmer, Lyle J. Penninx, Brenda Power, Chris Province, Michael A. Psaty, Bruce M. Qi, Lu Rauramaa, Rainer Ridker, Paul M. Ripatti, Samuli Salomaa, Veikko Samani, Nilesh J. Snieder, Harold Sorensen, Thorkild I. A. Spector, Timothy D. Stefansson, Kari Tonjes, Anke Tuomilehto, Jaakko Uitterlinden, Andre G. Uusitupa, Matti van der Harst, Pim Vollenweider, Peter Wallaschofski, Henri Wareham, Nicholas J. Watkins, Hugh Wichmann, H-Erich Wilson, James F. Abecasis, Goncalo R. Assimes, Themistocles L. Barroso, Ines Boehnke, Michael Borecki, Ingrid B. Deloukas, Panos Fox, Caroline S. Frayling, Timothy Groop, Leif C. Haritunian, Talin Heid, Iris M. Hunter, David Kaplan, Robert C. Karpe, Fredrik Moffatt, Miriam F. Mohlke, Karen L. O'Connell, Jeffrey R. Pawitan, Yudi Schadt, Eric E. Schlessinger, David Steinthorsdottir, Valgerdur Strachan, David P. Thorsteinsdottir, Unnur van Duijn, Cornelia M. Visscher, Peter M. Di Blasio, Anna Maria Hirschhorn, Joel N. Lindgren, Cecilia M. Morris, Andrew P. Meyre, David Scherag, Andr McCarthy, Mark I. Speliotes, Elizabeth K. North, Kari E. Loos, Ruth J. F. Ingelsson, Erik
Publication Year :
2013
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.
Details
Database :
OAIster
Notes :
application/pdf, English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1234206670
Document Type :
Electronic Resource
Full Text :
https://doi.org/10.1038.ng.2606