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The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study.

Thomas W Winkler Anne E Justice Mariaelisa Graff Llilda Barata Mary F Feitosa 1 Su Chu 2 Jacek Czajkowski Tõnu Esko 3, 4 Tove Fall 5 Tuomas O Kilpeläinen 6 Yingchang Lu 7 Reedik Mägi Evelin Mihailov Tune H Pers 8 Sina Rüeger Alexander Teumer 9 Georg B Ehret Teresa Ferreira Nancy L Heard-Costa Juha Karjalainen Vasiliki Lagou Anubha Mahajan Michael D Neinast Inga Prokopenko Jeannette Simino Tanya M Teslovich Rick Jansen 10 Harm-Jan Westra Charles C White 11 Devin Absher Tarunveer S Ahluwalia Shafqat Ahmad 12 Eva Albrecht Alexessander Couto Alves Jennifer L Bragg-Gresham 13 Anton J M de Craen 14 Joshua C Bis 15 Amélie Bonnefond 16 Gabrielle Boucher Gemma Cadby Yu-Ching Cheng Charleston W K Chiang Graciela Delgado Ayse Demirkan 17 Nicole Dueker Niina Eklund Gudny Eiriksdottir Joel Eriksson 18 Bjarke Feenstra Krista Fischer 19 Francesca Frau Tessel E Galesloot Frank Geller Anuj Goel Mathias Gorski Tanja B Grammer Stefan Gustafsson 20 Saskia Haitjema Jouke-Jan Hottenga 9 Jennifer E Huffman Anne U Jackson 21 Kevin B Jacobs 22, 23 Åsa Johansson Marika Kaakinen 24 Marcus E Kleber Jari Lahti Irene Mateo Leach Benjamin Lehne Youfang Liu Ken Sin Lo 25 Mattias Lorentzon Jian'An Luan Pamela a F Madden 26 Massimo Mangino 9 Barbara Mcknight Carolina Medina-Gomez Keri L Monda 27 May E Montasser Gabriele Müller Martina Müller-Nurasyid Ilja M Nolte 9 Kalliope Panoutsopoulou 28 Laura Pascoe Lavinia Paternoster Nigel W Rayner 28 Frida Renström 29, 30, 31 Federica Rizzi Lynda M Rose Kathy A Ryan Perttu Salo Serena Sanna Hubert Scharnagl Jianxin Shi Albert Vernon Smith Lorraine Southam 28 Alena Stančáková 32 Valgerdur Steinthorsdottir Rona J Strawbridge 33 Yun Ju Sung 34 Ioanna Tachmazidou Toshiko Tanaka 35 Gudmar Thorleifsson 36 Stella Trompet 37 Natalia Pervjakova Jonathan P Tyrer Liesbeth Vandenput Sander W van der Laan Nathalie van der Velde Jessica van Setten Jana V van Vliet-Ostaptchouk 38 Niek Verweij Efthymia Vlachopoulou Lindsay L Waite Sophie R Wang Zhaoming Wang Sarah H Wild Christina Willenborg James F Wilson Andrew Wong Jian Yang Loïc Yengo 16 Laura M Yerges-Armstrong Lei Yu Weihua Zhang Jing Hua Zhao Ehm A Andersson Stephan J L Bakker 39 Damiano Baldassarre Karina Banasik Matteo Barcella Cristina Barlassina Claire Bellis Paola Benaglio John Blangero 40, 41 Matthias Blüher 42 Fabrice Bonnet 43 Lori L Bonnycastle Heather A Boyd 44 Marcel Bruinenberg Aron S Buchman Harry Campbell 45 Yii-Der Ida Chen Peter S Chines Simone Claudi-Boehm John Cole 46 Francis S Collins Eco J C de Geus 47 Lisette C P G M de Groot Maria Dimitriou Jubao Duan 48 Stefan Enroth Elodie Eury 16 Aliki-Eleni Farmaki Nita G Forouhi 49 Nele Friedrich Pablo V Gejman Bruna Gigante Nicola Glorioso Alan S Go Omri Gottesman Jürgen Gräßler Harald Grallert 50 Niels Grarup 51 Yu-Mei Gu 52 Linda Broer 9 Annelies C Ham Torben Hansen 51 Tamara B Harris Catharina A Hartman 47 Maija Hassinen Nicholas Hastie Andrew T Hattersley Andrew C Heath Anjali K Henders Dena Hernandez 53 Hans Hillege 54 Oddgeir Holmen Kees G Hovingh Jennie Hui Lise L Husemoen Nina Hutri-Kähönen Pirro G Hysi Thomas Illig 55 Philip L de Jager 56, 57, 58 Shapour Jalilzadeh Torben Jørgensen 59, 60, 61 J Wouter Jukema 37 Markus Juonala Stavroula Kanoni 62 Maria Karaleftheri Kay Tee Khaw Leena Kinnunen Steven J Kittner Wolfgang Koenig Ivana Kolcic 63 Peter Kovacs Nikolaj T Krarup Wolfgang Kratzer Janine Krüger Diana Kuh 64 Meena Kumari 65 Theodosios Kyriakou Claudia Langenberg 49 Lars Lannfelt 66 Chiara Lanzani Vaneet Lotay Lenore J Launer Karin Leander Jaana Lindström Allan Linneberg 67 Yan-Ping Liu Stéphane Lobbens 68 Robert Luben 69 Valeriya Lyssenko Satu Männistö 70 Patrik K Magnusson Wendy L Mcardle Cristina Menni Sigrun Merger Lili Milani Grant W Montgomery 71, 17 Andrew P Morris Narisu Narisu Mari Nelis Ken K Ong 72 Aarno Palotie 73 Louis Pérusse 31 Irene Pichler Maria G Pilia Anneli Pouta Myriam Rheinberger Rasmus Ribel-Madsen Marcus Richards 74 Kenneth M Rice 75 Treva K Rice Carlo Rivolta Veikko Salomaa 76 Alan R Sanders Mark A Sarzynski Salome Scholtens Robert A Scott William R Scott Sylvain Sebert Sebanti Sengupta Bengt Sennblad Thomas Seufferlein Angela Silveira P Eline Slagboom 77 Jan H Smit Thomas H Sparsø Kathleen Stirrups Ronald P Stolk Heather M Stringham 13 Morris A Swertz 78 Amy J Swift Ann-Christine Syvänen 79 Sian-Tsung Tan Barbara Thorand 50 Anke Tönjes Angelo Tremblay 80 Emmanouil Tsafantakis Peter J van der Most Uwe Völker 81 Marie-Claude Vohl Judith M Vonk Melanie Waldenberger Ryan W Walker Roman Wennauer Elisabeth Widén 47 Gonneke Willemsen 17 Tom Wilsgaard Alan F Wright M Carola Zillikens 82, 83 Suzanne C van Dijk Natasja M van Schoor Folkert W Asselbergs Paul I W de Bakker Jacques S Beckmann 84 John Beilby David A Bennett 85 Richard N Bergman Sven Bergmann 86 Carsten A Böger Bernhard O Boehm Eric Boerwinkle 40 Dorret I Boomsma 9 Stefan R Bornstein 87 Erwin P Bottinger Claude Bouchard John C Chambers 88 Stephen J Chanock 23 Daniel I Chasman 89 Francesco Cucca Daniele Cusi 90, 91 George Dedoussis 62 Jeanette Erdmann 92 Johan G Eriksson 18 Denis A Evans 93 Ulf de Faire Martin Farrall 94 Luigi Ferrucci 95 Ian Ford Lude Franke Paul W Franks Philippe Froguel 16, 85 Ron T Gansevoort 96 Christian Gieger 97 Henrik Grönberg 5 Vilmundur Gudnason 98, 99 Ulf Gyllensten 100 Per Hall Anders Hamsten 101 Pim van der Harst Caroline Hayward 100 Markku Heliövaara Christian Hengstenberg 102 Andrew A Hicks Aroon Hingorani Albert Hofman 103 Frank Hu Heikki V Huikuri 104 Kristian Hveem Alan L James Joanne M Jordan 105 Antti Jula Mika Kähönen 106 Eero Kajantie Sekar Kathiresan Lambertus a L M Kiemeney 9 Mika Kivimaki 107, 65 Paul B Knekt Heikki A Koistinen 108 Jaspal S Kooner 85 Seppo Koskinen 109 Johanna Kuusisto 32 Winfried Maerz Nicholas G Martin Markku Laakso 32 Timo A Lakka 110 Terho Lehtimäki 111 Guillaume Lettre 112 Douglas F Levinson 113 Lars Lind Marja-Liisa Lokki Pekka Mäntyselkä Mads Melbye 44 Andres Metspalu 3, 4 Braxton D Mitchell Frans L Moll Jeffrey C Murray 114 Arthur W Musk Markku S Nieminen Inger Njølstad Claes Ohlsson 115 Albertine J Oldehinkel 116 Ben A Oostra 103 Lyle J Palmer James S Pankow Gerard Pasterkamp 117 Nancy L Pedersen 118 Oluf Pedersen 51, 119 Brenda W Penninx 17 Markus Perola 120, 121 Annette Peters Ozren Polašek 100 Peter P Pramstaller 100 Bruce M Psaty 122, 123, 124, 125, 126 Lu Qi Thomas Quertermous Olli T Raitakari 127, 128 Tuomo Rankinen Rainer Rauramaa Paul M Ridker 89 John D Rioux Fernando Rivadeneira 129 Jerome I Rotter 130 Igor Rudan 100 Hester M den Ruijter Juha Saltevo Naveed Sattar 131 Heribert Schunkert 92 Peter E H Schwarz Alan R Shuldiner Juha Sinisalo Harold Snieder 132, 133 Thorkild I A Sørensen 134, 51 Tim D Spector 9 Jan A Staessen 135 Bandinelli Stefania Unnur Thorsteinsdottir 36 Michael Stumvoll Jean-Claude Tardif Elena Tremoli Jaakko Tuomilehto 136, 137, 138 André G Uitterlinden 139, 103 Matti Uusitupa 140 André L M Verbeek 141 Sita H Vermeulen Jorma S Viikari 142 Veronique Vitart 100 Henry Völzke 143 Peter Vollenweider Gérard Waeber 144 Mark Walker Henri Wallaschofski Nicholas J Wareham 145 Hugh Watkins Eleftheria Zeggini 28 Aravinda Chakravarti 9 Deborah J Clegg L Adrienne Cupples 146 Penny Gordon-Larsen Cashell E Jaquish D C Rao Goncalo R Abecasis 47 Themistocles L Assimes Inês Barroso 147, 148 Sonja I Berndt Michael Boehnke 13 Panos Deloukas 28 Caroline S Fox Leif C Groop 30 David J Hunter Erik Ingelsson 5 Robert C Kaplan Mark I Mccarthy Karen L Mohlke 149 Jeffrey R O'Connell 150 David Schlessinger 47 David P Strachan Kari Stefansson 36 Cornelia M van Duijn 103 Joel N Hirschhorn 151, 152 Cecilia M Lindgren 94, 153 Iris M Heid 154 Kari E North 155 Ingrid B Borecki 1 Zoltán Kutalik 156 Ruth J F Loos 157
Abstract : Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and WHRadjBMI in four strata (men ≤50y, men >50y, women ≤50y, women >50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR<5%) age-specific effects, of which 11 had larger effects in younger (<50y) than in older adults (≥50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may provide further insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.
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https://hal-univ-rennes1.archives-ouvertes.fr/hal-01218025
Contributeur : Laurent Jonchère <>
Soumis le : mardi 20 octobre 2015 - 14:39:58
Dernière modification le : lundi 20 juillet 2020 - 13:06:04

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Thomas W Winkler, Anne E Justice, Mariaelisa Graff, Llilda Barata, Mary F Feitosa, et al.. The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study.. PLoS Genetics, Public Library of Science, 2015, 11 (10), pp.e1005378. ⟨10.1371/journal.pgen.1005378⟩. ⟨hal-01218025⟩

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