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

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Winkler , T W , Justice , A E , Graff , M , Barata , L , Feitosa , M F , Chu , S , Czajkowski , J , Esko , T , Fall , T , Kilpelainen , T O , Lu , Y , Magi , R , Mihailov , E , Pers , T H , Rueeger , S , Teumer , A , Ehret , G B , Ferreira , T , Heard-Costa , N L , Karjalainen , J , Lagou , V , Mahajan , A , Neinast , M D , Prokopenko , I , Simino , J , Teslovich , T M , Jansen , R , Westra , H-J , White , C C , Absher , D , Ahluwalia , T S , Ahmad , S , Albrecht , E , Alves , A C , Bragg-Gresham , J L , de Craen , A J M , Bis , J C , Bonnefond , A , Boucher , G , Cadby , G , Cheng , Y-C , Chiang , C W K , Delgado , G , Demirkan , A , Dueker , N , Eklund , N , Eiriksdottir , G , Eriksson , J , Feenstra , B , Fischer , K , Frau , F , Galesloot , T E , Geller , F , Goel , A , Gorski , M , Grammer , T B , Gustafsson , S , Haitjema , S , Hottenga , J-J , Huffman , J E , Jackson , A U , Jacobs , K B , Johansson , A , Kaakinen , M , Kleber , M E , Lahti , J , Leach , I M , Lehne , B , Liu , Y , Lo , K S , Lorentzon , M , Luan , J , Madden , P A F , Mangino , M , McKnight , B , Medina-Gomez , C , Monda , K L , Montasser , M E , Mueller , G , Mueller-Nurasyid , M , Nolte , I M , Panoutsopoulou , K , Pascoe , L , Paternoster , L , Rayner , N W , Renstrom , F , Rizzi , F , Rose , L M , Ryan , K A , Salo , P , Sanna , S , Scharnagl , H , Shi , J , Smith , A V , Southam , L , Stancakova , A , Steinthorsdottir , V , Strawbridge , R J , Sung , Y J , Tachmazidou , I , Tanaka , T , Thorleifsson , G , Trompet , S , Pervjakova , N , Tyrer , J P , Vandenput , L , van der Laan , S W , van der Velde , N , van Setten , J , van Vliet-Ostaptchouk , J V , Verweij , N , Vlachopoulou , E , Waite , L L , Wang , S R , Wang , Z , Wild , S H , Willenborg , C , Wilson , J F , Wong , A , Yang , J , Yengo , L , Yerges-Armstrong , L M , Yu , L , Zhang , W , Zhao , J H , Andersson , E A , Bakker , S J L , Baldassarre , D , Banasik , K , Barcella , M , Barlassina , C , Bellis , C , Benaglio , P , Blangero , J , Blueher , M , Bonnet , F , Bonnycastle , L L , Boyd , H A , Bruinenberg , M , Buchman , A S , Campbell , H , Chen , Y-D I , Chines , P S , Claudi-Boehm , S , Cole , J , Collins , F S , de Geus , E J C , de Groot , L C P G M , Dimitriou , M , Duan , J , Enroth , S , Eury , E , Farmaki , A-E , Forouhi , N G , Friedrich , N , Gejman , P V , Gigante , B , Glorioso , N , Go , A S , Gottesman , O , Graessler , J , Grallert , H , Grarup , N , Gu , Y-M , Broer , L , Ham , A C , Hansen , T , Harris , T B , Hartman , C A , Hassinen , M , Hastie , N , Hattersley , A T , Heath , A C , Henders , A K , Hernandez , D , Hillege , H , Holmen , O , Hovingh , K G , Hui , J , Husemoen , L L , Hutri-Kahonen , N , Hysi , P G , Illig , T , De Jager , P L , Jalilzadeh , S , Jorgensen , T , Jukema , J W , Juonala , M , Kanoni , S , Karaleftheri , M , Khaw , K T , Kinnunen , L , Kittner , S J , Koenig , W , Kolcic , I , Kovacs , P , Krarup , N T , Kratzer , W , Krueger , J , Kuh , D , Kumari , M , Kyriakou , T , Langenberg , C , Lannfelt , L , Lanzani , C , Lotay , V , Launer , L J , Leander , K , Lindstrom , J , Linneberg , A , Liu , Y-P , Lobbens , S , Luben , R , Lyssenko , V , Mannisto , S , Magnusson , P K , McArdle , W L , Menni , C , Merger , S , Milani , L , Montgomery , G W , Morris , A P , Narisu , N , Nelis , M , Ong , K K , Palotie , A , Perusse , L , Pichler , I , Pilia , M G , Pouta , A , Rheinberger , M , Ribel-Madsen , R , Richards , M , Rice , K M , Rice , T K , Rivolta , C , Salomaa , V , Sanders , A R , Sarzynski , M A , Scholtens , S , Scott , R A , Scott , W R , Sebert , S , Sengupta , S , Sennblad , B , Seufferlein , T , Silveira , A , Slagboom , P E , Smit , J H , Sparso , T H , Stirrups , K , Stolk , R P , Stringham , H M , Swertz , M A , Swift , A J , Syvanen , A-C , Tan , S-T , Thorand , B , Toenjes , A , Tremblay , A , Tsafantakis , E , van der Most , P J , Voelker , U , Vohl , M-C , Vonk , J M , Waldenberger , M , Walker , R W , Wennauer , R , Widen , E , Willemsen , G , Wilsgaard , T , Wright , A F , Zillikens , M C , van Dijk , S C , van Schoor , N M , Asselbergs , F W , de Bakker , P I W , Beckmann , J S , Beilby , J , Bennett , D A , Bergman , R N , Bergmann , S , Boeger , C A , Boehm , B O , Boerwinkle , E , Boomsma , D I , Bornstein , S R , Bottinger , E P , Bouchard , C , Chambers , J C , Chanock , S J , Chasman , D I , Cucca , F , Cusi , D , Dedoussis , G , Erdmann , J , Eriksson , J G , Evans , D A , de Faire , U , Farrall , M , Ferrucci , L , Ford , I , Franke , L , Franks , P W , Froguel , P , Gansevoort , R T , Gieger , C , Gronberg , H , Gudnason , V , Gyllensten , U , Hall , P , Hamsten , A , van der Harst , P , Hayward , C , Heliovaara , M , Hengstenberg , C , Hicks , A A , Hingorani , A , Hofman , A , Hu , F , Huikuri , H V , Hveem , K , James , A L , Jordan , J M , Jula , A , Kaehoenen , M , Kajantie , E , Kathiresan , S , Kiemeney , L A L M , Kivimaki , M , Knekt , P B , Koistinen , H A , Kooner , J S , Koskinen , S , Kuusisto , J , Maerz , W , Martin , N G , Laakso , M , Lakka , T A , Lehtimaki , T , Lettre , G , Levinson , D F , Lind , L , Lokki , M-L , Mantyselka , P , Melbye , M , Metspalu , A , Mitchell , B D , Moll , F L , Murray , J C , Musk , A W , Nieminen , M S , Njolstad , I , Ohlsson , C , Oldehinkel , A J , Oostra , B A , Palmer , L J , Pankow , J S , Pasterkamp , G , Pedersen , N L , Pedersen , O , Penninx , B W , Perola , M , Peters , A , Polasek , O , Pramstaller , P P , Psaty , B M , Qi , L , Quertermous , T , Raitakari , O T , Rankinen , T , Rauramaa , R , Ridker , P M , Rioux , J D , Rivadeneira , F , Rotter , J I , Rudan , I , den Ruijter , H M , Saltevo , J , Sattar , N , Schunkert , H , Schwarz , P E H , Shuldiner , A R , Sinisalo , J , Snieder , H , Sorensen , T I A , Spector , T D , Staessen , J A , Stefania , B , Thorsteinsdottir , U , Stumvoll , M , Tardif , J-C , Tremoli , E , Tuomilehto , J , Uitterlinden , A G , Uusitupa , M , Verbeek , A L M , Vermeulen , S H , Viikari , J S , Vitart , V , Voelzke , H , Vollenweider , P , Waeber , G , Walker , M , Wallaschofski , H , Wareham , N J , Watkins , H , Zeggini , E , Chakravarti , A , Clegg , D J , Cupples , L A , Gordon-Larsen , P , Jaquish , C E , Rao , D C , Abecasis , G R , Assimes , T L , Barroso , I , Berndt , S I , Boehnke , M , Deloukas , P , Fox , C S , Groop , L C , Hunter , D J , Ingelsson , E , Kaplan , R C , McCarthy , M I , Mohlke , K L , O'Connell , J R , Schlessinger , D , Strachan , D P , Stefansson , K , van Duijn , C M , Hirschhorn , J N , Lindgren , C M , Heid , I M , North , K E , Borecki , I B , Kutalik , Z & Loos , R J F 2015 , ' The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape : A Large-Scale Genome-Wide Interaction Study ' , PLoS Genetics , vol. 11 , no. 10 , 1005378 . https://doi.org/10.1371/journal.pgen.1005378

Title: The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape : A Large-Scale Genome-Wide Interaction Study
Author: Winkler, Thomas W.; Justice, Anne E.; Graff, Mariaelisa; Barata, Llilda; Feitosa, Mary F.; Chu, Su; Czajkowski, Jacek; Esko, Tonu; Fall, Tove; Kilpelainen, Tuomas O.; Lu, Yingchang; Magi, Reedik; Mihailov, Evelin; Pers, Tune H.; Rueeger, 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, Amelie; 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, Asa; Kaakinen, Marika; Kleber, Marcus E.; Lahti, Jari; Leach, Irene Mateo; 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.; Mueller, Gabriele; Mueller-Nurasyid, Martina; Nolte, Ilja M.; Panoutsopoulou, Kalliope; Pascoe, Laura; Paternoster, Lavinia; Rayner, Nigel W.; Renstrom, Frida; Rizzi, Federica; Rose, Lynda M.; Ryan, Kathy A.; Salo, Perttu; Sanna, Serena; Scharnagl, Hubert; Shi, Jianxin; Smith, Albert Vernon; Southam, Lorraine; Stancakova, 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, Loic; 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; Blueher, 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; Graessler, Juergen; 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-Kahonen, Nina; Hysi, Pirro G.; Illig, Thomas; De Jager, Philip L.; Jalilzadeh, Shapour; Jorgensen, 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; Krueger, Janine; Kuh, Diana; Kumari, Meena; Kyriakou, Theodosios; Langenberg, Claudia; Lannfelt, Lars; Lanzani, Chiara; Lotay, Vaneet; Launer, Lenore J.; Leander, Karin; Lindstrom, Jaana; Linneberg, Allan; Liu, Yan-Ping; Lobbens, Stephane; Luben, Robert; Lyssenko, Valeriya; Mannisto, 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; Perusse, 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.; Sparso, Thomas H.; Stirrups, Kathleen; Stolk, Ronald P.; Stringham, Heather M.; Swertz, Morris A.; Swift, Amy J.; Syvanen, Ann-Christine; Tan, Sian-Tsung; Thorand, Barbara; Toenjes, Anke; Tremblay, Angelo; Tsafantakis, Emmanouil; van der Most, Peter J.; Voelker, Uwe; Vohl, Marie-Claude; Vonk, Judith M.; Waldenberger, Melanie; Walker, Ryan W.; Wennauer, Roman; Widen, 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; Boeger, 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 W.; Froguel, Philippe; Gansevoort, Ron T.; Gieger, Christian; Gronberg, Henrik; Gudnason, Vilmundur; Gyllensten, Ulf; Hall, Per; Hamsten, Anders; van der Harst, Pim; Hayward, Caroline; Heliovaara, 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; Kaehoenen, 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.; Lehtimaki, Terho; Lettre, Guillaume; Levinson, Douglas F.; Lind, Lars; Lokki, Marja-Liisa; Mantyselka, Pekka; Melbye, Mads; Metspalu, Andres; Mitchell, Braxton D.; Moll, Frans L.; Murray, Jeffrey C.; Musk, Arthur W.; Nieminen, Markku S.; Njolstad, 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; Polasek, 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; Sorensen, Thorkild I. A.; Spector, Tim D.; Staessen, Jan A.; Stefania, Bandinelli; Thorsteinsdottir, Unnur; Stumvoll, Michael; Tardif, Jean-Claude; Tremoli, Elena; Tuomilehto, Jaakko; Uitterlinden, Andre G.; Uusitupa, Matti; Verbeek, Andre L. M.; Vermeulen, Sita H.; Viikari, Jorma S.; Vitart, Veronique; Voelzke, Henry; Vollenweider, Peter; Waeber, Gerard; 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, Ines; Berndt, Sonja I.; Boehnke, Michael; Deloukas, Panos; Fox, Caroline S.; Groop, Leif C.; 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, Zoltan; Loos, Ruth J. F.
Contributor: University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Helsinki Collegium for Advanced Studies
University of Helsinki, University of Helsinki
University of Helsinki, Transplantation Laboratory
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Clinicum
University of Helsinki, Children's Hospital
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Clinicum
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Medicum
University of Helsinki, Clinicum
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Clinicum
University of Helsinki, Institute for Molecular Medicine Finland
University of Helsinki, Institute for Molecular Medicine Finland
Date: 2015-10
Language: eng
Number of pages: 42
Belongs to series: PLoS Genetics
ISSN: 1553-7404
URI: http://hdl.handle.net/10138/158846
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 similar to 2.8M SNPs with BMI and WHRadjBMI in four strata (men 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 providefurther insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.
Subject: SELF-REPORTED HEIGHT
FAT DISTRIBUTION
MASS INDEX
LIFE-COURSE
BIOLOGICAL PATHWAYS
NATURAL MENOPAUSE
PERIPHERAL-BLOOD
WEIGHT-GAIN
COMMON SNPS
LOCI
3111 Biomedicine
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