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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.
Authors :
Winkler, Thomas W 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 Mihailov, Evelin Pers, Tune H Rüeger, Sina 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 Jansen, Rick Westra, Harm-Jan White, Charles C 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 Cheng, Yu-Ching Chiang, Charleston W K Delgado, Graciela Demirkan, Ayse Dueker, Nicole Eklund, Niina Eiriksdottir, Gudny Eriksson, Joel Feenstra, Bjarke Fischer, Krista Frau, Francesca Galesloot, Tessel E Geller, Frank Goel, Anuj Gorski, Mathias Grammer, Tanja B 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 Lehne, Benjamin Liu, Youfang Lo, Ken Sin 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 Panoutsopoulou, Kalliope Pascoe, Laura Paternoster, Lavinia 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 Stančáková, Alena Steinthorsdottir, Valgerdur Strawbridge, Rona J 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 van Vliet-Ostaptchouk, Jana V Verweij, Niek Vlachopoulou, Efthymia Waite, Lindsay L Wang, Sophie R Wang, Zhaoming Wild, Sarah H Willenborg, Christina Wilson, James F Wong, Andrew Yang, Jian Yengo, Loïc Yerges-Armstrong, Laura M Yu, Lei Zhang, Weihua Zhao, Jing Hua 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 Bonnycastle, Lori L Boyd, Heather A Bruinenberg, Marcel 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 Enroth, Stefan Eury, Elodie Farmaki, Aliki-Eleni 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 Broer, Linda Ham, Annelies C 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 Hovingh, Kees G Hui, Jennie Husemoen, Lise L 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 Kinnunen, Leena Kittner, Steven J Koenig, Wolfgang Kolcic, Ivana Kovacs, Peter Krarup, Nikolaj T Kratzer, Wolfgang Krüger, Janine Kuh, Diana Kumari, Meena Kyriakou, Theodosios Langenberg, Claudia Lannfelt, Lars Lanzani, Chiara Lotay, Vaneet Launer, Lenore J Leander, Karin Lindström, Jaana Linneberg, Allan Liu, Yan-Ping Lobbens, Stéphane Luben, Robert Lyssenko, Valeriya Männistö, Satu Magnusson, Patrik K McArdle, Wendy L Menni, Cristina Merger, Sigrun Milani, Lili Montgomery, Grant W 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 Richards, Marcus Rice, Kenneth M Rice, Treva K 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 Silveira, Angela Slagboom, P Eline Smit, Jan H 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 Tsafantakis, Emmanouil van der Most, Peter J Völker, Uwe 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 van Schoor, Natasja M Asselbergs, Folkert W 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 Bottinger, Erwin P Bouchard, Claude Chambers, John C 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 Ford, Ian Franke, Lude Franks, Paul 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 Hengstenberg, Christian Hicks, Andrew A Hingorani, Aroon 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 Kivimaki, Mika Knekt, Paul B 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 Lind, Lars Lokki, Marja-Liisa Mäntyselkä, Pekka 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 Palmer, Lyle J Pankow, James S Pasterkamp, Gerard Pedersen, Nancy L Pedersen, Oluf Penninx, Brenda W Perola, Markus Peters, Annette Polašek, Ozren Pramstaller, Peter P Psaty, Bruce M Qi, Lu Quertermous, Thomas Raitakari, Olli T Rankinen, Tuomo Rauramaa, Rainer Ridker, Paul M 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 Snieder, Harold Sørensen, Thorkild I A Spector, Tim D Staessen, Jan A Stefania, Bandinelli Thorsteinsdottir, Unnur Stumvoll, Michael Tardif, Jean-Claude Tremoli, Elena Tuomilehto, Jaakko Uitterlinden, André G Uusitupa, Matti Verbeek, André L M Vermeulen, Sita H Viikari, Jorma S Vitart, Veronique Völzke, Henry Vollenweider, Peter Waeber, Gérard Walker, Mark Wallaschofski, Henri Wareham, Nicholas J Watkins, Hugh Zeggini, Eleftheria Chakravarti, Aravinda Clegg, Deborah J Cupples, L Adrienne Gordon-Larsen, Penny Jaquish, Cashell E Rao, D C Abecasis, Goncalo R Assimes, Themistocles L Barroso, Inês Berndt, Sonja I Boehnke, Michael Deloukas, Panos Fox, Caroline S Groop, Leif Hunter, David J Ingelsson, Erik Kaplan, Robert C McCarthy, Mark I Mohlke, Karen L 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 Loos, Ruth J F Winkler, Thomas W 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 Mihailov, Evelin Pers, Tune H Rüeger, Sina 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 Jansen, Rick Westra, Harm-Jan White, Charles C 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 Cheng, Yu-Ching Chiang, Charleston W K Delgado, Graciela Demirkan, Ayse Dueker, Nicole Eklund, Niina Eiriksdottir, Gudny Eriksson, Joel Feenstra, Bjarke Fischer, Krista Frau, Francesca Galesloot, Tessel E Geller, Frank Goel, Anuj Gorski, Mathias Grammer, Tanja B 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 Lehne, Benjamin Liu, Youfang Lo, Ken Sin 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 Panoutsopoulou, Kalliope Pascoe, Laura Paternoster, Lavinia 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 Stančáková, Alena Steinthorsdottir, Valgerdur Strawbridge, Rona J 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 van Vliet-Ostaptchouk, Jana V Verweij, Niek Vlachopoulou, Efthymia Waite, Lindsay L Wang, Sophie R Wang, Zhaoming Wild, Sarah H Willenborg, Christina Wilson, James F Wong, Andrew Yang, Jian Yengo, Loïc Yerges-Armstrong, Laura M Yu, Lei Zhang, Weihua Zhao, Jing Hua 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 Bonnycastle, Lori L Boyd, Heather A Bruinenberg, Marcel 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 Enroth, Stefan Eury, Elodie Farmaki, Aliki-Eleni 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 Broer, Linda Ham, Annelies C 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 Hovingh, Kees G Hui, Jennie Husemoen, Lise L 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 Kinnunen, Leena Kittner, Steven J Koenig, Wolfgang Kolcic, Ivana Kovacs, Peter Krarup, Nikolaj T Kratzer, Wolfgang Krüger, Janine Kuh, Diana Kumari, Meena Kyriakou, Theodosios Langenberg, Claudia Lannfelt, Lars Lanzani, Chiara Lotay, Vaneet Launer, Lenore J Leander, Karin Lindström, Jaana Linneberg, Allan Liu, Yan-Ping Lobbens, Stéphane Luben, Robert Lyssenko, Valeriya Männistö, Satu Magnusson, Patrik K McArdle, Wendy L Menni, Cristina Merger, Sigrun Milani, Lili Montgomery, Grant W 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 Richards, Marcus Rice, Kenneth M Rice, Treva K 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 Silveira, Angela Slagboom, P Eline Smit, Jan H 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 Tsafantakis, Emmanouil van der Most, Peter J Völker, Uwe 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 van Schoor, Natasja M Asselbergs, Folkert W 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 Bottinger, Erwin P Bouchard, Claude Chambers, John C 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 Ford, Ian Franke, Lude Franks, Paul 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 Hengstenberg, Christian Hicks, Andrew A Hingorani, Aroon 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 Kivimaki, Mika Knekt, Paul B 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 Lind, Lars Lokki, Marja-Liisa Mäntyselkä, Pekka 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 Palmer, Lyle J Pankow, James S Pasterkamp, Gerard Pedersen, Nancy L Pedersen, Oluf Penninx, Brenda W Perola, Markus Peters, Annette Polašek, Ozren Pramstaller, Peter P Psaty, Bruce M Qi, Lu Quertermous, Thomas Raitakari, Olli T Rankinen, Tuomo Rauramaa, Rainer Ridker, Paul M 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 Snieder, Harold Sørensen, Thorkild I A Spector, Tim D Staessen, Jan A Stefania, Bandinelli Thorsteinsdottir, Unnur Stumvoll, Michael Tardif, Jean-Claude Tremoli, Elena Tuomilehto, Jaakko Uitterlinden, André G Uusitupa, Matti Verbeek, André L M Vermeulen, Sita H Viikari, Jorma S Vitart, Veronique Völzke, Henry Vollenweider, Peter Waeber, Gérard Walker, Mark Wallaschofski, Henri Wareham, Nicholas J Watkins, Hugh Zeggini, Eleftheria Chakravarti, Aravinda Clegg, Deborah J Cupples, L Adrienne Gordon-Larsen, Penny Jaquish, Cashell E Rao, D C Abecasis, Goncalo R Assimes, Themistocles L Barroso, Inês Berndt, Sonja I Boehnke, Michael Deloukas, Panos Fox, Caroline S Groop, Leif Hunter, David J Ingelsson, Erik Kaplan, Robert C McCarthy, Mark I Mohlke, Karen L 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 Loos, Ruth J F
Source :
PLoS Genetics; 11(10), no e1005378 (2015); ISSN: 1553-7404
Publication Year :
2015
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.
Details
Database :
OAIster
Journal :
PLoS Genetics; 11(10), no e1005378 (2015); ISSN: 1553-7404
Notes :
application/pdf, English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1023427175
Document Type :
Electronic Resource