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

Publication

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

Journal Paper/Review - Oct 1, 2015

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

Citation

Asselbergs F, Chanock S, Chasman D, Cucca F, Cusi D, Dedoussis G, Erdmann J, Eriksson J, Evans D, de Faire U, Farrall M, Ferrucci L, Chambers J, Bouchard C, Bottinger E, de Bakker P, Beckmann J, Beilby J, Bennett D, Bergman R, Bergmann S, Böger C, Boehm B, Boerwinkle E, Boomsma D, Bornstein S, Ford I, Franke L, Franks P, Hofman A, Hu F, Huikuri H, Hveem K, James A, Jordan J, Jula A, Kähönen M, Kajantie E, Kathiresan S, Kiemeney L, Hingorani A, Hicks A, Hengstenberg C, Froguel P, Gansevoort R, Gieger C, Grönberg H, Gudnason V, Gyllensten U, Hall P, Hamsten A, van der Harst P, Hayward C, Heliövaara M, Kivimäki M, Montgomery G, Rivolta C, Salomaa V, Sanders A, Sarzynski M, Scholtens S, Scott R, Scott W, Sebert S, Sengupta S, Sennblad B, Seufferlein T, Rice T, Rice K, Richards M, Morris A, Narisu N, Nelis M, Ong K, Palotie A, Pérusse L, Pichler I, Pilia M, Pouta A, Rheinberger M, Ribel-Madsen R, Silveira A, Slagboom P, Smit J, Vohl M, Vonk J, Waldenberger M, Walker R, Wennauer R, Widén E, Willemsen G, Wilsgaard T, Wright A, Zillikens M, van Dijk S, Völker U, van der Most P, Tsafantakis E, Sparsø T, Stirrups K, Stolk R, Stringham H, Swertz M, Swift A, Syvänen A, Tan S, Thorand B, Tönjes A, Tremblay A, van Schoor N, Sørensen T, Völzke H, Vollenweider P, Waeber G, Walker M, Wallaschofski H, Wareham N, Watkins H, Zeggini E, Chakravarti A, Clegg D, Vitart V, Viikari J, Vermeulen S, Spector T, Staessen J, Bandinelli S, Thorsteinsdottir U, Stumvoll M, Tardif J, Tremoli E, Tuomilehto J, Uitterlinden A, Uusitupa M, Verbeek A, Cupples L, Gordon-Larsen P, Jaquish C, O'Connell J, Schlessinger D, Strachan D, Stefansson K, van Duijn C, Hirschhorn J, Lindgren C, Heid I, North K, Borecki I, Kutalik Z, Mohlke K, McCarthy M, Kaplan R, Rao D, Abecasis G, Assimes T, Barroso I, Berndt S, Boehnke M, Deloukas P, Fox C, Groop L, Hunter D, Ingelsson E, Loos R, Knekt P, Melbye M, Metspalu A, Mitchell B, Moll F, Murray J, Musk A, Nieminen M, Njølstad I, Ohlsson C, Oldehinkel A, Oostra B, Mäntyselkä P, Lokki M, Lind L, Koistinen H, Kooner J, Koskinen S, Kuusisto J, Maerz W, Martin N, Laakso M, Lakka T, Lehtimäki T, Lettre G, Levinson D, Palmer L, Pankow J, Pasterkamp G, Rioux J, Rivadeneira F, Rotter J, Rudan I, den Ruijter H, Saltevo J, Sattar N, Schunkert H, Schwarz P, Shuldiner A, Sinisalo J, Ridker P, Rauramaa R, Rankinen T, Pedersen N, Pedersen O, Penninx B, Perola M, Peters A, Polasek O, Pramstaller P, Psaty B, Qi L, Quertermous T, Raitakari O, Snieder H, Grammer T, Lorentzon M, Luan J, Madden P, Mangino M, McKnight B, Medina-Gomez C, Monda K, Montasser M, Müller G, Müller-Nurasyid M, Nolte I, Lo K, Liu Y, Lehne B, Gustafsson S, Haitjema S, Hottenga J, Huffman J, Jackson A, Jacobs K, Johansson Å, Kaakinen M, Kleber M, Lahti J, Mateo Leach I, Panoutsopoulou K, Pascoe L, Paternoster L, Sung Y, Tachmazidou I, Tanaka T, Thorleifsson G, Trompet S, Pervjakova N, Tyrer J, Vandenput L, van der Laan S, van der Velde N, van Setten J, Strawbridge R, Steinthorsdottir V, Stančáková A, Rayner N, Renström F, Rizzi F, Rose L, Ryan K, Salo P, Sanna S, Scharnagl H, Shi J, Smith A, Southam L, van Vliet-Ostaptchouk J, Winkler T, Teumer A, Ehret G, Ferreira T, Heard-Costa N, Karjalainen J, Lagou V, Mahajan A, Neinast M, Prokopenko I, Simino J, Teslovich T, Rüeger S, Pers T, Mihailov E, Justice A, Graff M, Barata L, Feitosa M, Chu S, Czajkowski J, Esko T, Fall T, Kilpeläinen T, Lu Y, Mägi R, Jansen R, Westra H, White C, Demirkan A, Dueker N, Eklund N, Eiriksdottir G, Eriksson J, Feenstra B, Fischer K, Frau F, Galesloot T, Geller F, Goel A, Delgado G, Chiang C, Cheng Y, Absher D, Ahluwalia T, Ahmad S, Albrecht E, Alves A, Bragg-Gresham J, de Craen A, Bis J, Bonnefond A, Boucher G, Cadby G, Gorski M, Ham A, Hutri-Kähönen N, Hysi P, Illig T, De Jager P, Jalilzadeh S, Jørgensen T, Jukema J, Juonala M, Kanoni S, Karaleftheri M, Khaw K, Husemoen L, Hui J, Hovingh K, Hansen T, Harris T, Hartman C, Hassinen M, Hastie N, Hattersley A, Heath A, Henders A, Hernandez D, Hillege H, Holmen O, Kinnunen L, Kittner S, Koenig W, Lindström J, Linneberg A, Liu Y, Lobbens S, Luben R, Lyssenko V, Männistö S, Magnusson P, McArdle W, Menni C, Merger S, Leander K, Launer L, Lotay V, Kolcic I, Kovacs P, Krarup N, Kratzer W, Krüger J, Kuh D, Kumari M, Kyriakou T, Langenberg C, Lannfelt L, Lanzani C, Milani L, Verweij N, Andersson E, Bakker S, Baldassarre D, Banasik K, Barcella M, Barlassina C, Bellis C, Benaglio P, Blangero J, Blüher M, Bonnet F, Zhao J, Zhang W, Yu L, Vlachopoulou E, Waite L, Wang S, Wang Z, Wild S, Willenborg C, Wilson J, Wong A, Yang J, Yengo L, Yerges-Armstrong L, Bonnycastle L, Boyd H, Bruinenberg M, Forouhi N, Friedrich N, Gejman P, Gigante B, Glorioso N, Go A, Gottesman O, Gräßler J, Grallert H, Grarup N, Gu Y, Farmaki A, Eury E, Enroth S, Buchman A, Campbell H, Chen Y, Chines P, Claudi-Boehm S, Cole J, Collins F, de Geus E, de Groot L, Dimitriou M, Duan J, Broer L. The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study. PLoS Genet 2015; 11:e1005378.

Type

Journal Paper/Review (English)

Journal

PLoS Genet 2015; 11

Publication Date

Oct 1, 2015

Issn Electronic

1553-7404

Pages

e1005378

Brief description/objective

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.