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

  • Sonja I Berndt
  • , Stefan Gustafsson
  • , Tonu Esko
  • , Jean Ferrieres
  • , Lude Franke
  • , Francesca Frau
  • , Pablo V Gejman
  • , Harald Grallert
  • , Henrik Gronberg
  • , Vilmundur Gudnason
  • , Alistair S Hall
  • , Per Hall
  • , Anna-Liisa Hartikainen
  • , Tove Fall
  • , Caroline Hayward
  • , Nancy L Heard-Costa
  • , Andrew C Heath
  • , Johannes Hebebrand
  • , Georg Homuth
  • , Frank B Hu
  • Sarah E Hunt, Elina Hypponen, Carlos Iribarren, Kevin B Jacobs, Teresa Ferreira, John-Olov Jansson, Antti Jula, Mika Kahonen, Sekar Kathiresan, Frank Kee, Kay-Tee Khaw, Mika Kivimaki, Wolfgang Koenig, Aldi T Kraja, Meena Kumari, Davide Gentilini, Kari Kuulasmaa, Johanna Kuusisto, Jaana H Laitinen, Timo A Lakka, Claudia Langenberg, Lenore J Launer, Lars Lind, Jaana Lindstrom, Jianjun Liu, Antonio Liuzzi, Anne U Jackson, Marja-Liisa Lokki, Mattias Lorentzon, Pamela A Madden, Patrik K Magnusson, Paolo Manunta, Diana Marek, Winfried Marz, Irene Mateo Leach, Barbara McKnight, Sarah E Medland, Jian'an Luan, Evelin Mihailov, Lili Milani, Grant W Montgomery, Vincent Mooser, Thomas W Muhleisen, Patricia B Munroe, Arthur W Musk, Narisu Narisu, Gerjan Navis, George Nicholson, Joshua C Randall, 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, Sailaja Vedantam, Peter P Pramstaller, Inga Prokopenko, Carolin Putter, Aparna Radhakrishnan, Olli Raitakari, Augusto Rendon, Fernando Rivadeneira, Igor Rudan, Timo E Saaristo, Jennifer G Sambrook, Cristen J Willer, Alan R Sanders, Serena Sanna, Jouko Saramies, Sabine Schipf, Stefan Schreiber, Heribert Schunkert, So-Youn Shin, Stefano Signorini, Juha Sinisalo, Boris Skrobek, Thomas W Winkler, Nicole Soranzo, Alena Stancakova, Klaus Stark, Jonathan C Stephens, Kathleen Stirrups, Ronald P Stolk, Michael Stumvoll, Amy J Swift, Eirini V Theodoraki, Barbara Thorand, Reedik Magi, Andrew R Wood, David-Alexandre Tregouet, Elena Tremoli, Melanie M Van der Klauw, Joyce B J van Meurs, Sita H Vermeulen, Jorma Viikari, Jarmo Virtamo, Veronique Vitart, Gerard Waeber, Zhaoming Wang, Tsegaselassie Workalemahu, Elisabeth Widen, 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, Yi-Juan Hu, 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, Sang Hong Lee, Paul W Franks, Philippe Froguel, Christian Gieger, Ulf Gyllensten, Anders Hamsten, Tamara B Harris, Christian Hengstenberg, Andrew A Hicks, Aroon Hingorani, Anke Hinney, Liming Liang, Albert Hofman, Kees G Hovingh, Kristian Hveem, Thomas Illig, Marjo-Riitta Jarvelin, Karl-Heinz Jockel, Sirkka M Keinanen-Kiukaanniemi, Lambertus A Kiemeney, Diana Kuh, Markku Laakso, Dan-Yu Lin, Terho Lehtimaki, Douglas F Levinson, Nicholas G Martin, Andres Metspalu, Andrew D Morris, Markku S Nieminen, Inger Njolstad, Claes Ohlsson, Albertine J Oldehinkel, Willem H Ouwehand, Josine L Min, Lyle J Palmer, Brenda Penninx, Chris Power, Michael A Province, Bruce M Psaty, Lu Qi, Rainer Rauramaa, Paul M Ridker, Samuli Ripatti, Veikko Salomaa, Benjamin M Neale, Nilesh J Samani, Harold Snieder, Thorkild I A Sorensen, Timothy D Spector, Kari Stefansson, Anke Tonjes, Jaakko Tuomilehto, Andre G Uitterlinden, Matti Uusitupa, Pim van der Harst, Gudmar Thorleifsson, Peter Vollenweider, Henri Wallaschofski, Nicholas J Wareham, Hugh Watkins, H-Erich Wichmann, James F Wilson, Goncalo R Abecasis, Themistocles L Assimes, Ines Barroso, Michael Boehnke, Jian Yang, 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, Andrea Ganna, Eva Albrecht, 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, Najaf Amin, Peter M Visscher, Anna Maria Di Blasio, Joel N Hirschhorn, Cecilia M Lindgren, Andrew P Morris, David Meyre, Andre Scherag, Mark I McCarthy, Elizabeth K Speliotes, Kari E North, Jennifer L Bragg-Gresham, Ruth J F Loos, Erik Ingelsson, Gemma Cadby, Martin den Heijer, Niina Eklund, Krista Fischer, Anuj Goel, Jouke-Jan Hottenga, Jennifer E Huffman, Eleanor Wheeler, Ivonne Jarick, Asa Johansson, Toby Johnson, Stavroula Kanoni, Marcus E Kleber, Inke R Konig, Kati Kristiansson, Zoltan Kutalik, Claudia Lamina, Cecile Lecoeur, Mary F Feitosa, Guo Li, Massimo Mangino, Wendy L McArdle, Carolina Medina-Gomez, Martina Muller-Nurasyid, Julius S Ngwa, Ilja M Nolte, Lavinia Paternoster, Sonali Pechlivanis, Markus Perola, Anne E Justice, 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, Keri L Monda, 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, Damien C Croteau-Chonka, 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, Felix R Day, 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

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

548 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.
Original languageEnglish
Pages (from-to)501-512
JournalNature Genetics
Volume45
Issue number5
DOIs
Publication statusPublished - 2013

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

  1. SDG 3 - Good Health and Well-being
    SDG 3 Good Health and Well-being

Keywords

  • Gene Expression (incl. Microarray and other genome-wide approaches)

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