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

Dmitry Shungin 1, 2, 3 Thomas W Winkler Damien C Croteau-Chonka Teresa Ferreira 4 Adam E Locke Reedik Mägi Rona J Strawbridge 5 Tune H Pers 6 Krista Fischer Anne E Justice Tsegaselassie Workalemahu Joseph M W Wu 7 Martin L Buchkovich Nancy L Heard-Costa Tamara S Roman Alexander W Drong Ci Song Stefan Gustafsson 8 Felix R Day Tonu Esko 9, 10 Tove Fall 11 Zoltán Kutalik 12 Jian'An Luan Joshua C Randall André Scherag 13 Sailaja Vedantam Andrew R Wood Jin Chen Rudolf Fehrmann Juha Karjalainen Bratati Kahali Ching-Ti Liu Ellen M Schmidt 14 Devin Absher Najaf Amin 15 Denise Anderson 16 Marian Beekman Jennifer L Bragg-Gresham 17 Steven Buyske Ayse Demirkan 15 Georg B Ehret Mary F Feitosa 18 Anuj Goel Anne U Jackson Toby Johnson Marcus E Kleber Kati Kristiansson Massimo Mangino 19 Irene Mateo Leach Carolina Medina-Gomez Cameron D Palmer Dorota Pasko Sonali Pechlivanis Marjolein J Peters Inga Prokopenko Alena Stančáková 20 Yun Ju Sung Toshiko Tanaka Alexander Teumer 19 Jana V van Vliet-Ostaptchouk 21 Loïc Yengo 22 Weihua Zhang Eva Albrecht Johan Ärnlöv Gillian M Arscott Stefania Bandinelli 23 Amy Barrett 24 Claire Bellis Amanda J Bennett Christian Berne Matthias Blüher 25 Stefan Böhringer Fabrice Bonnet 26 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 27, 28 Elodie Eury Nele Friedrich Melissa E Garcia Vilmantas Giedraitis Bruna Gigante Alan S Go Alain Golay Harald Grallert 29 Tanja B Grammer Jürgen Gräßler Jagvir Grewal Christopher J Groves Toomas Haller Goran Hallmans 30 Catharina A Hartman 31 Maija Hassinen Caroline Hayward 32 Kauko Heikkilä 33 Karl-Heinz Herzig Quinta Helmer Hans L Hillege 34 Oddgeir Holmen Steven C Hunt Aaron Isaacs 19 Till Ittermann Alan L James 35 Ingegerd Johansson 36 Thorhildur Juliusdottir Ioanna-Panagiota Kalafati Leena Kinnunen Wolfgang Koenig Ishminder K Kooner Wolfgang Kratzer Claudia Lamina Karin Leander Nanette R Lee Peter Lichtner 37 Lars Lind Jaana Lindström Stéphane Lobbens 38 Mattias Lorentzon François Mach 39 Patrik K E Magnusson 40 Anubha Mahajan 41 Wendy L Mcardle Cristina Menni Sigrun Merger Evelin Mihailov Lili Milani Rebecca Mills Alireza Moayyeri Keri L Monda 42 Simon P Mooijaart Thomas W Mühleisen 43, 44 Antonella Mulas Gabriele Müller Martina Müller-Nurasyid Ramaiah Nagaraja 45 Michael A Nalls 46 Narisu Narisu Nicola Glorioso Ilja M Nolte 19 Matthias Olden Nigel W Rayner 47 Frida Renstrom 48, 1, 2 Janina S Ried 49 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 17 Johan Sundström 50 Morris A Swertz 51 Amy J Swift Ann-Christine Syvänen 5 Bamidele O Tayo Barbara Thorand 29 Gudmar Thorleifsson 52 Andreas Tomaschitz Chiara Troffa Floor V A van Oort Niek Verweij Judith M Vonk 53 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 54 Fredrik Karpe Sarah Keildson Krzysztof Kiryluk Liming Liang Richard P Lifton 55 Baoshan Ma Amy J Mcknight Ruth Mcpherson Andres Metspalu 9, 10 Josine L Min Miriam F Moffatt 56 Grant W Montgomery 15, 57 Joanne M Murabito George Nicholson 58 Dale R Nyholt 31 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 59 Dominique Arveiler 60 Stephan J L Bakker 61 John Beilby Richard N Bergman John Blangero Morris J Brown Michel Burnier Harry Campbell Aravinda Chakravarti 19 Peter S Chines Simone Claudi-Boehm Francis S Collins Dana C Crawford John Danesh 62 Ulf de Faire Eco J C de Geus 31 Marcus Dörr Raimund Erbel 63 Johan G Eriksson Martin Farrall 64 Ele Ferrannini 65 Jean Ferrières Nita G Forouhi 66 Terrence Forrester Oscar H Franco 67 Ron T Gansevoort 68 Christian Gieger 69 Vilmundur Gudnason 70, 71 Christopher A Haiman Tamara B Harris 72 Andrew T Hattersley Markku Heliövaara Andrew A Hicks 73 Aroon D Hingorani Wolfgang Hoffmann 74 Albert Hofman 75, 15 Georg Homuth 76 Steve E Humphries 77 Elina Hyppönen 78, 79 Thomas Illig 80 Marjo-Riitta Jarvelin 81, 82, 83 Berit Johansen Pekka Jousilahti Antti M Jula Jaakko Kaprio 15 Frank Kee 84 Sirkka M Keinanen-Kiukaanniemi Jaspal S Kooner 85 Charles Kooperberg Peter Kovacs 86 Aldi T Kraja Meena Kumari 87 Kari Kuulasmaa Johanna Kuusisto 20 Timo A Lakka 88 Claudia Langenberg 66 Loic Le Marchand 89 Terho Lehtimäki 90 Valeriya Lyssenko Satu Männistö 91 André Marette 92 Tara C Matise Colin A Mckenzie Barbara Mcknight Arthur W Musk Stefan Möhlenkamp 63 Andrew D Morris Mari Nelis Claes Ohlsson 93 Albertine J Oldehinkel 94 Ken K Ong 95 Lyle J Palmer Brenda W Penninx 15 Annette Peters Peter P Pramstaller 32 Olli T Raitakari 96, 97 Tuomo Rankinen D C Rao Treva K Rice Paul M Ridker 98 Marylyn D Ritchie Igor Rudan 32 Veikko Salomaa 99 Nilesh J Samani 100, 101 Jouko Saramies Mark A Sarzynski Peter E H Schwarz Alan R Shuldiner Jan A Staessen 102 Valgerdur Steinthorsdottir Ronald P Stolk Konstantin Strauch Anke Tönjes Angelo Tremblay Elena Tremoli Marie-Claude Vohl Uwe Völker 76 Peter Vollenweider James F Wilson Jacqueline C Witteman 19 Linda S Adair Murielle Bochud 103 Bernhard O Boehm Stefan R Bornstein 104 Claude Bouchard 105 Stéphane Cauchi 106 Mark J Caulfield 107 John C Chambers Daniel I Chasman 98 Richard S Cooper George Dedoussis 54 Luigi Ferrucci 31 Philippe Froguel 108 Hans-Jörgen Grabe 109 Anders Hamsten 110 Jennie Hui Kristian Hveem Karl-Heinz Jöckel 111 Mika Kivimaki 87 Diana Kuh 112 Markku Laakso 20 Yongmei Liu Winfried März 113 Patricia B Munroe 107 Inger Njølstad Ben A Oostra 19 Colin N A Palmer Nancy L Pedersen 114 Markus Perola 115, 116 Louis Pérusse 2 Ulrike Peters Chris Power Thomas Quertermous Rainer Rauramaa Fernando Rivadeneira 27 Timo E Saaristo Danish Saleheen Juha Sinisalo P Eline Slagboom Harold Snieder 117, 118 Tim D Spector 19 Unnur Thorsteinsdottir 52 Michael Stumvoll Jaakko Tuomilehto 119, 120, 121 André G Uitterlinden 122, 75, 15 Matti Uusitupa 123 Pim van der Harst Giovanni Veronesi Mark Walker Nicholas J Wareham 124 Hugh Watkins H-Erich Wichmann 125 Goncalo R Abecasis 31 Themistocles L Assimes Sonja I Berndt 126 Michael Boehnke 17 Ingrid B Borecki 18 Panos Deloukas 47 Lude Franke Timothy M Frayling 127 Leif C Groop 1 David J Hunter Robert C Kaplan Jeffrey R O'Connell Lu Qi David Schlessinger 31 David P Strachan Kari Stefansson 52 Cornelia M van Duijn Cristen J Willer Peter M Visscher 128 Jian Yang 129 Joel N Hirschhorn 130, 131 M Carola Zillikens 122, 75 Mark I Mccarthy Elizabeth K Speliotes Kari E North 132 Caroline S Fox Inês Barroso 133, 134 Paul W Franks Erik Ingelsson 11 Iris M Heid 135 Ruth J F Loos 136 L Adrienne Cupples 137 Andrew P Morris Cecilia M Lindgren 64, 138 Karen L Mohlke 139
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.
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https://hal-univ-rennes1.archives-ouvertes.fr/hal-01132692
Contributor : Laurent Jonchère <>
Submitted on : Tuesday, March 17, 2015 - 5:01:13 PM
Last modification on : Thursday, October 22, 2020 - 3:09:53 AM

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Dmitry Shungin, Thomas W Winkler, Damien C Croteau-Chonka, Teresa Ferreira, Adam E Locke, et al.. New genetic loci link adipose and insulin biology to body fat distribution.. Nature, Nature Publishing Group, 2015, 518 (7538), pp.187-96. ⟨10.1038/nature14132⟩. ⟨hal-01132692⟩

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