학술논문
The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study.
Document Type
article
Author
Thomas W Winkler; Anne E Justice; Mariaelisa Graff; Llilda Barata; Mary F Feitosa; Su Chu; Jacek Czajkowski; Tõnu Esko; Tove Fall; Tuomas O Kilpeläinen; Yingchang Lu; Reedik Mägi; Evelin Mihailov; Tune H Pers; Sina Rüeger; Alexander Teumer; 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; Harm-Jan Westra; Charles C White; Devin Absher; Tarunveer S Ahluwalia; Shafqat Ahmad; Eva Albrecht; Alexessander Couto Alves; Jennifer L Bragg-Gresham; Anton J M de Craen; Joshua C Bis; Amélie Bonnefond; Gabrielle Boucher; Gemma Cadby; Yu-Ching Cheng; Charleston W K Chiang; Graciela Delgado; Ayse Demirkan; Nicole Dueker; Niina Eklund; Gudny Eiriksdottir; Joel Eriksson; Bjarke Feenstra; Krista Fischer; Francesca Frau; Tessel E Galesloot; Frank Geller; Anuj Goel; Mathias Gorski; Tanja B Grammer; Stefan Gustafsson; Saskia Haitjema; Jouke-Jan Hottenga; Jennifer E Huffman; Anne U Jackson; Kevin B Jacobs; Åsa Johansson; Marika Kaakinen; Marcus E Kleber; Jari Lahti; Irene Mateo Leach; Benjamin Lehne; Youfang Liu; Ken Sin Lo; Mattias Lorentzon; Jian'an Luan; Pamela A F Madden; Massimo Mangino; Barbara McKnight; Carolina Medina-Gomez; Keri L Monda; May E Montasser; Gabriele Müller; Martina Müller-Nurasyid; Ilja M Nolte; Kalliope Panoutsopoulou; Laura Pascoe; Lavinia Paternoster; Nigel W Rayner; Frida Renström; Federica Rizzi; Lynda M Rose; Kathy A Ryan; Perttu Salo; Serena Sanna; Hubert Scharnagl; Jianxin Shi; Albert Vernon Smith; Lorraine Southam; Alena Stančáková; Valgerdur Steinthorsdottir; Rona J Strawbridge; Yun Ju Sung; Ioanna Tachmazidou; Toshiko Tanaka; Gudmar Thorleifsson; Stella Trompet; Natalia Pervjakova; Jonathan P Tyrer; Liesbeth Vandenput; Sander W van der Laan; Nathalie van der Velde; Jessica van Setten; Jana V van Vliet-Ostaptchouk; 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; Laura M Yerges-Armstrong; Lei Yu; Weihua Zhang; Jing Hua Zhao; Ehm A Andersson; Stephan J L Bakker; Damiano Baldassarre; Karina Banasik; Matteo Barcella; Cristina Barlassina; Claire Bellis; Paola Benaglio; John Blangero; Matthias Blüher; Fabrice Bonnet; Lori L Bonnycastle; Heather A Boyd; Marcel Bruinenberg; Aron S Buchman; Harry Campbell; Yii-Der Ida Chen; Peter S Chines; Simone Claudi-Boehm; John Cole; Francis S Collins; Eco J C de Geus; Lisette C P G M de Groot; Maria Dimitriou; Jubao Duan; Stefan Enroth; Elodie Eury; Aliki-Eleni Farmaki; Nita G Forouhi; Nele Friedrich; Pablo V Gejman; Bruna Gigante; Nicola Glorioso; Alan S Go; Omri Gottesman; Jürgen Gräßler; Harald Grallert; Niels Grarup; Yu-Mei Gu; Linda Broer; Annelies C Ham; Torben Hansen; Tamara B Harris; Catharina A Hartman; Maija Hassinen; Nicholas Hastie; Andrew T Hattersley; Andrew C Heath; Anjali K Henders; Dena Hernandez; Hans Hillege; Oddgeir Holmen; Kees G Hovingh; Jennie Hui; Lise L Husemoen; Nina Hutri-Kähönen; Pirro G Hysi; Thomas Illig; Philip L De Jager; Shapour Jalilzadeh; Torben Jørgensen; J Wouter Jukema; Markus Juonala; Stavroula Kanoni; Maria Karaleftheri; Kay Tee Khaw; Leena Kinnunen; Steven J Kittner; Wolfgang Koenig; Ivana Kolcic; Peter Kovacs; Nikolaj T Krarup; Wolfgang Kratzer; Janine Krüger; Diana Kuh; Meena Kumari; Theodosios Kyriakou; Claudia Langenberg; Lars Lannfelt; Chiara Lanzani; Vaneet Lotay; Lenore J Launer; Karin Leander; Jaana Lindström; Allan Linneberg; Yan-Ping Liu; Stéphane Lobbens; Robert Luben; Valeriya Lyssenko; Satu Männistö; Patrik K Magnusson; Wendy L McArdle; Cristina Menni; Sigrun Merger; Lili Milani; Grant W Montgomery; Andrew P Morris; Narisu Narisu; Mari Nelis; Ken K Ong; Aarno Palotie; Louis Pérusse; Irene Pichler; Maria G Pilia; Anneli Pouta; Myriam Rheinberger; Rasmus Ribel-Madsen; Marcus Richards; Kenneth M Rice; Treva K Rice; Carlo Rivolta; Veikko Salomaa; 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; Jan H Smit; Thomas H Sparsø; Kathleen Stirrups; Ronald P Stolk; Heather M Stringham; Morris A Swertz; Amy J Swift; Ann-Christine Syvänen; Sian-Tsung Tan; Barbara Thorand; Anke Tönjes; Angelo Tremblay; Emmanouil Tsafantakis; Peter J van der Most; Uwe Völker; Marie-Claude Vohl; Judith M Vonk; Melanie Waldenberger; Ryan W Walker; Roman Wennauer; Elisabeth Widén; Gonneke Willemsen; Tom Wilsgaard; Alan F Wright; M Carola Zillikens; Suzanne C van Dijk; Natasja M van Schoor; Folkert W Asselbergs; Paul I W de Bakker; Jacques S Beckmann; John Beilby; David A Bennett; Richard N Bergman; Sven Bergmann; Carsten A Böger; Bernhard O Boehm; Eric Boerwinkle; Dorret I Boomsma; Stefan R Bornstein; Erwin P Bottinger; Claude Bouchard; John C Chambers; Stephen J Chanock; Daniel I Chasman; Francesco Cucca; Daniele Cusi; George Dedoussis; Jeanette Erdmann; Johan G Eriksson; Denis A Evans; Ulf de Faire; Martin Farrall; Luigi Ferrucci; Ian Ford; Lude Franke; Paul W Franks; Philippe Froguel; Ron T Gansevoort; Christian Gieger; Henrik Grönberg; Vilmundur Gudnason; Ulf Gyllensten; Per Hall; Anders Hamsten; Pim van der Harst; Caroline Hayward; Markku Heliövaara; Christian Hengstenberg; Andrew A Hicks; Aroon Hingorani; Albert Hofman; Frank Hu; Heikki V Huikuri; Kristian Hveem; Alan L James; Joanne M Jordan; Antti Jula; Mika Kähönen; Eero Kajantie; Sekar Kathiresan; Lambertus A L M Kiemeney; Mika Kivimaki; Paul B Knekt; Heikki A Koistinen; Jaspal S Kooner; Seppo Koskinen; Johanna Kuusisto; Winfried Maerz; Nicholas G Martin; Markku Laakso; Timo A Lakka; Terho Lehtimäki; Guillaume Lettre; Douglas F Levinson; Lars Lind; Marja-Liisa Lokki; Pekka Mäntyselkä; Mads Melbye; Andres Metspalu; Braxton D Mitchell; Frans L Moll; Jeffrey C Murray; Arthur W Musk; Markku S Nieminen; Inger Njølstad; Claes Ohlsson; Albertine J Oldehinkel; Ben A Oostra; Lyle J Palmer; James S Pankow; Gerard Pasterkamp; Nancy L Pedersen; Oluf Pedersen; Brenda W Penninx; Markus Perola; Annette Peters; Ozren Polašek; Peter P Pramstaller; Bruce M Psaty; Lu Qi; Thomas Quertermous; Olli T Raitakari; Tuomo Rankinen; Rainer Rauramaa; Paul M Ridker; John D Rioux; Fernando Rivadeneira; Jerome I Rotter; Igor Rudan; Hester M den Ruijter; Juha Saltevo; Naveed Sattar; Heribert Schunkert; Peter E H Schwarz; Alan R Shuldiner; Juha Sinisalo; Harold Snieder; Thorkild I A Sørensen; Tim D Spector; Jan A Staessen; Bandinelli Stefania; Unnur Thorsteinsdottir; Michael Stumvoll; Jean-Claude Tardif; Elena Tremoli; Jaakko Tuomilehto; André G Uitterlinden; Matti Uusitupa; André L M Verbeek; Sita H Vermeulen; Jorma S Viikari; Veronique Vitart; Henry Völzke; Peter Vollenweider; Gérard Waeber; Mark Walker; Henri Wallaschofski; Nicholas J Wareham; Hugh Watkins; Eleftheria Zeggini; CHARGE Consortium; DIAGRAM Consortium; GLGC Consortium; Global-BPGen Consortium; ICBP Consortium; MAGIC Consortium; Aravinda Chakravarti; Deborah J Clegg; L Adrienne Cupples; Penny Gordon-Larsen; Cashell E Jaquish; D C Rao; Goncalo R Abecasis; Themistocles L Assimes; Inês Barroso; Sonja I Berndt; Michael Boehnke; Panos Deloukas; Caroline S Fox; Leif C Groop; David J Hunter; Erik Ingelsson; Robert C Kaplan; Mark I McCarthy; Karen L Mohlke; Jeffrey R O'Connell; David Schlessinger; David P Strachan; Kari Stefansson; Cornelia M van Duijn; Joel N Hirschhorn; Cecilia M Lindgren; Iris M Heid; Kari E North; Ingrid B Borecki; Zoltán Kutalik; Ruth J F Loos
Source
PLoS Genetics, Vol 11, Iss 10, p e1005378 (2015)
Subject
Language
English
ISSN
1553-7390
1553-7404
1553-7404
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