New genetic loci link adipose and insulin biology to body fat distribution.

Authors:
Dmitry Shungin, Thomas W Winkler, Damien C Croteau-Chonka, Teresa Ferreira, Adam E Locke, Reedik Mägi, Rona J Strawbridge, Tune H Pers, Krista Fischer, Anne E Justice, Tsegaselassie Workalemahu, Joseph M W Wu, Martin L Buchkovich, Nancy L Heard-Costa, Tamara S Roman, Alexander W Drong, Ci Song, Stefan Gustafsson, Felix R Day, Tonu Esko, Tove Fall, Zoltán Kutalik, Jian'an Luan, Joshua C Randall, André Scherag, Sailaja Vedantam, Andrew R Wood, Jin Chen, Rudolf Fehrmann, Juha Karjalainen, Bratati Kahali, Ching-Ti Liu, Ellen M Schmidt, Devin Absher, Najaf Amin, Denise Anderson, Marian Beekman, Jennifer L Bragg-Gresham, Steven Buyske, Ayse Demirkan, Georg B Ehret, Mary F Feitosa, Anuj Goel, Anne U Jackson, Toby Johnson, Marcus E Kleber, Kati Kristiansson, Massimo Mangino, Irene Mateo Leach, Carolina Medina-Gomez, Cameron D Palmer, Dorota Pasko, Sonali Pechlivanis, Marjolein J Peters, Inga Prokopenko, Alena Stančáková, Yun Ju Sung, Toshiko Tanaka, Alexander Teumer, Jana V Van Vliet-Ostaptchouk, Loïc Yengo, Weihua Zhang, Eva Albrecht, Johan Ärnlöv, Gillian M Arscott, Stefania Bandinelli, Amy Barrett, Claire Bellis, Amanda J Bennett, Christian Berne, Matthias Blüher, Stefan Böhringer, Fabrice Bonnet, Yvonne Böttcher, Marcel Bruinenberg, Delia B Carba, Ida H Caspersen, Robert Clarke, E Warwick Daw, Joris Deelen, Ewa Deelman, Graciela Delgado, Alex S F Doney, Niina Eklund, Michael R Erdos, Karol Estrada, Elodie Eury, Nele Friedrich, Melissa E Garcia, Vilmantas Giedraitis, Bruna Gigante, Alan S Go, Alain Golay, Harald Grallert, Tanja B Grammer, Jürgen Gräßler, Jagvir Grewal, Christopher J Groves, Toomas Haller, Goran Hallmans, Catharina A Hartman, Maija Hassinen, Caroline Hayward, Kauko Heikkilä, Karl-Heinz Herzig, Quinta Helmer, Hans L Hillege, Oddgeir Holmen, Steven C Hunt, Aaron Isaacs, Till Ittermann, Alan L James, Ingegerd Johansson, Thorhildur Juliusdottir, Ioanna-Panagiota Kalafati, Leena Kinnunen, Wolfgang Koenig, Ishminder K Kooner, Wolfgang Kratzer, Claudia Lamina, Karin Leander, Nanette R Lee, Peter Lichtner, Lars Lind, Jaana Lindström, Stéphane Lobbens, Mattias Lorentzon, François Mach, Patrik K E Magnusson, Anubha Mahajan, Wendy L McArdle, Cristina Menni, Sigrun Merger, Evelin Mihailov, Lili Milani, Rebecca Mills, Alireza Moayyeri, Keri L Monda, Simon P Mooijaart, Thomas W Mühleisen, Antonella Mulas, Gabriele Müller, Martina Müller-Nurasyid, Ramaiah Nagaraja, Michael A Nalls, Narisu Narisu, Nicola Glorioso, Ilja M Nolte, Matthias Olden, Nigel W Rayner, Frida Renstrom, Janina S Ried, Neil R Robertson, Lynda M Rose, Serena Sanna, Hubert Scharnagl, Salome Scholtens, Bengt Sennblad, Thomas Seufferlein, Colleen M Sitlani, Albert Vernon Smith, Kathleen Stirrups, Heather M Stringham, Johan Sundström, Morris A Swertz, Amy J Swift, Ann-Christine Syvänen, Bamidele O Tayo, Barbara Thorand, Gudmar Thorleifsson, Andreas Tomaschitz, Chiara Troffa, Floor V A van Oort, Niek Verweij, Judith M Vonk, Lindsay L Waite, Roman Wennauer, Tom Wilsgaard, Mary K Wojczynski, Andrew Wong, Qunyuan Zhang, Jing Hua Zhao, Eoin P Brennan, Murim Choi, Per Eriksson, Lasse Folkersen, Anders Franco-Cereceda, Ali G Gharavi, Åsa K Hedman, Marie-France Hivert, Jinyan Huang, Stavroula Kanoni, Fredrik Karpe, Sarah Keildson, Krzysztof Kiryluk, Liming Liang, Richard P Lifton, Baoshan Ma, Amy J McKnight, Ruth McPherson, Andres Metspalu, Josine L Min, Miriam F Moffatt, Grant W Montgomery, Joanne M Murabito, George Nicholson, Dale R Nyholt, Christian Olsson, John R B Perry, Eva Reinmaa, Rany M Salem, Niina Sandholm, Eric E Schadt, Robert A Scott, Lisette Stolk, Edgar E Vallejo, Harm-Jan Westra, Krina T Zondervan, - -, Philippe Amouyel, Dominique Arveiler, Stephan J L Bakker, John Beilby, Richard N Bergman, John Blangero, Morris J Brown, Michel Burnier, Harry Campbell, Aravinda Chakravarti, Peter S Chines, Simone Claudi-Boehm, Francis S Collins, Dana C Crawford, John Danesh, Ulf de Faire, Eco J C de Geus, Marcus Dörr, Raimund Erbel, Johan G Eriksson, Martin Farrall, Ele Ferrannini, Jean Ferrières, Nita G Forouhi, Terrence Forrester, Oscar H Franco, Ron T Gansevoort, Christian Gieger, Vilmundur Gudnason, Christopher A Haiman, Tamara B Harris, Andrew T Hattersley, Markku Heliövaara, Andrew A Hicks, Aroon D Hingorani, Wolfgang Hoffmann, Albert Hofman, Georg Homuth, Steve E Humphries, Elina Hyppönen, Thomas Illig, Marjo-Riitta Jarvelin, Berit Johansen, Pekka Jousilahti, Antti M Jula, Jaakko Kaprio, Frank Kee, Sirkka M Keinanen-Kiukaanniemi, Jaspal S Kooner, Charles Kooperberg, Peter Kovacs, Aldi T Kraja, Meena Kumari, Kari Kuulasmaa, Johanna Kuusisto, Timo A Lakka, Claudia Langenberg, Loic Le Marchand, Terho Lehtimäki, Valeriya Lyssenko, Satu Männistö, André Marette, Tara C Matise, Colin A McKenzie, Barbara McKnight, Arthur W Musk, Stefan Möhlenkamp, Andrew D Morris, Mari Nelis, Claes Ohlsson, Albertine J Oldehinkel, Ken K Ong, Lyle J Palmer, Brenda W Penninx, Annette Peters, Peter P Pramstaller, Olli T Raitakari, Tuomo Rankinen, D C Rao, Treva K Rice, Paul M Ridker, Marylyn D Ritchie, Igor Rudan, Veikko Salomaa, Nilesh J Samani, Jouko Saramies, Mark A Sarzynski, Peter E H Schwarz, Alan R Shuldiner, Jan A Staessen, Valgerdur Steinthorsdottir, Ronald P Stolk, Konstantin Strauch, Anke Tönjes, Angelo Tremblay, Elena Tremoli, Marie-Claude Vohl, Uwe Völker, Peter Vollenweider, James F Wilson, Jacqueline C Witteman, Linda S Adair, Murielle Bochud, Bernhard O Boehm, Stefan R Bornstein, Claude Bouchard, Stéphane Cauchi, Mark J Caulfield, John C Chambers, Daniel I Chasman, Richard S Cooper, George Dedoussis, Luigi Ferrucci, Philippe Froguel, Hans-Jörgen Grabe, Anders Hamsten, Jennie Hui, Kristian Hveem, Karl-Heinz Jöckel, Mika Kivimaki, Diana Kuh, Markku Laakso, Yongmei Liu, Winfried März, Patricia B Munroe, Inger Njølstad, Ben A Oostra, Colin N A Palmer, Nancy L Pedersen, Markus Perola, Louis Pérusse, Ulrike Peters, Chris Power, Thomas Quertermous, Rainer Rauramaa, Fernando Rivadeneira, Timo E Saaristo, Danish Saleheen, Juha Sinisalo, P Eline Slagboom, Harold Snieder, Tim D Spector, Unnur Thorsteinsdottir, Michael Stumvoll, Jaakko Tuomilehto, André G Uitterlinden, Matti Uusitupa, Pim van der Harst, Giovanni Veronesi, Mark Walker, Nicholas J Wareham, Hugh Watkins, H-Erich Wichmann, Goncalo R Abecasis, Themistocles L Assimes, Sonja I Berndt, Michael Boehnke, Ingrid B Borecki, Panos Deloukas, Lude Franke, Timothy M Frayling, Leif C Groop, David J Hunter, Robert C Kaplan, Jeffrey R O'Connell, Lu Qi, David Schlessinger, David P Strachan, Kari Stefansson, Cornelia M van Duijn, Cristen J Willer, Peter M Visscher, Jian Yang, Joel N Hirschhorn, M Carola Zillikens, Mark I McCarthy, Elizabeth K Speliotes, Kari E North, Caroline S Fox, Inês Barroso, Paul W Franks, Erik Ingelsson, Iris M Heid, Ruth J F Loos, L Adrienne Cupples, Andrew P Morris, Cecilia M Lindgren, Karen L Mohlke
Year of publication:
2015
Volume:
518
Issue:
7538
Issn:
0028-0836
Journal title abbreviated:
NATURE
Journal title long:
Nature : a weekly illustrated journal of science
Impact factor:
38.138
Abstract:
Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.