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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.

Winkler, Thomas W; Justice, Anne E; Graff, Mariaelisa; Barata, Llilda; Feitosa, Mary F; Chu, Su; Czajkowski, Jacek; Esko, Tõnu; Fall, Tove and Kilpeläinen, Tuomas O, et al. (2015) In PLoS Genetics 11(10).
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,... (More)
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. (Less)
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PLoS Genetics
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  • pmid:26426971
  • wos:000364401600002
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1553-7404
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10.1371/journal.pgen.1005378
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English
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@article{88d6afd1-3ae0-45c4-959d-4c70090c263e,
  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 &gt;50y, women ≤50y, women &gt;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&lt;5%) age-specific effects, of which 11 had larger effects in younger (&lt;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.},
  articleno    = {e1005378},
  author       = {Winkler, Thomas W and Justice, Anne E and Graff, Mariaelisa and Barata, Llilda and Feitosa, Mary F and Chu, Su and Czajkowski, Jacek and Esko, Tõnu and Fall, Tove and Kilpeläinen, Tuomas O and Lu, Yingchang and Mägi, Reedik and Mihailov, Evelin and Pers, Tune H and Rüeger, Sina and Teumer, Alexander and Ehret, Georg B and Ferreira, Teresa and Heard-Costa, Nancy L and Karjalainen, Juha and Lagou, Vasiliki and Mahajan, Anubha and Neinast, Michael D and Prokopenko, Inga and Simino, Jeannette and Teslovich, Tanya M and Jansen, Rick and Westra, Harm-Jan and White, Charles C and Absher, Devin and Ahluwalia, Tarunveer S and Ahmad, Shafqat and Albrecht, Eva and Alves, Alexessander Couto and Bragg-Gresham, Jennifer L and de Craen, Anton J M and Bis, Joshua C and Bonnefond, Amélie and Boucher, Gabrielle and Cadby, Gemma and Cheng, Yu-Ching and Chiang, Charleston W K and Delgado, Graciela and Demirkan, Ayse and Dueker, Nicole and Eklund, Niina and Eiriksdottir, Gudny and Eriksson, Joel and Feenstra, Bjarke and Fischer, Krista and Frau, Francesca and Galesloot, Tessel E and Geller, Frank and Goel, Anuj and Gorski, Mathias and Grammer, Tanja B and Gustafsson, Stefan and Haitjema, Saskia and Hottenga, Jouke-Jan and Huffman, Jennifer E and Jackson, Anne U and Jacobs, Kevin B and Johansson, Åsa and Kaakinen, Marika and Kleber, Marcus E and Lahti, Jari and Mateo Leach, Irene and Lehne, Benjamin and Liu, Youfang and Lo, Ken Sin and Lorentzon, Mattias and Luan, Jian'an and Madden, Pamela A F and Mangino, Massimo and McKnight, Barbara and Medina-Gomez, Carolina and Monda, Keri L and Montasser, May E and Müller, Gabriele and Müller-Nurasyid, Martina and Nolte, Ilja M and Panoutsopoulou, Kalliope and Pascoe, Laura and Paternoster, Lavinia and Rayner, Nigel W and Renström, Frida and Rizzi, Federica and Rose, Lynda M and Ryan, Kathy A and Salo, Perttu and Sanna, Serena and Scharnagl, Hubert and Shi, Jianxin and Smith, Albert Vernon and Southam, Lorraine and 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and Chen, Yii-Der Ida and Chines, Peter S and Claudi-Boehm, Simone and Cole, John and Collins, Francis S and de Geus, Eco J C and de Groot, Lisette C P G M and Dimitriou, Maria and Duan, Jubao and Enroth, Stefan and Eury, Elodie and Farmaki, Aliki-Eleni and Forouhi, Nita G and Friedrich, Nele and Gejman, Pablo V and Gigante, Bruna and Glorioso, Nicola and Go, Alan S and Gottesman, Omri and Gräßler, Jürgen and Grallert, Harald and Grarup, Niels and Gu, Yu-Mei and Broer, Linda and Ham, Annelies C and Hansen, Torben and Harris, Tamara B and Hartman, Catharina A and Hassinen, Maija and Hastie, Nicholas and Hattersley, Andrew T and Heath, Andrew C and Henders, Anjali K and Hernandez, Dena and Hillege, Hans and Holmen, Oddgeir and Hovingh, Kees G and Hui, Jennie and Husemoen, Lise L and Hutri-Kähönen, Nina and Hysi, Pirro G and Illig, Thomas and De Jager, Philip L and Jalilzadeh, Shapour and Jørgensen, Torben and Jukema, J Wouter and Juonala, Markus and Kanoni, Stavroula and Karaleftheri, 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Johanna and Maerz, Winfried and Martin, Nicholas G and Laakso, Markku and Lakka, Timo A and Lehtimäki, Terho and Lettre, Guillaume and Levinson, Douglas F and Lind, Lars and Lokki, Marja-Liisa and Mäntyselkä, Pekka and Melbye, Mads and Metspalu, Andres and Mitchell, Braxton D and Moll, Frans L and Murray, Jeffrey C and Musk, Arthur W and Nieminen, Markku S and Njølstad, Inger and Ohlsson, Claes and Oldehinkel, Albertine J and Oostra, Ben A and Palmer, Lyle J and Pankow, James S and Pasterkamp, Gerard and Pedersen, Nancy L and Pedersen, Oluf and Penninx, Brenda W and Perola, Markus and Peters, Annette and Polašek, Ozren and Pramstaller, Peter P and Psaty, Bruce M and Qi, Lu and Quertermous, Thomas and Raitakari, Olli T and Rankinen, Tuomo and Rauramaa, Rainer and Ridker, Paul M and Rioux, John D and Rivadeneira, Fernando and Rotter, Jerome I and Rudan, Igor and den Ruijter, Hester M and Saltevo, Juha and Sattar, Naveed and Schunkert, Heribert and Schwarz, Peter E H and Shuldiner, Alan R 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and Strachan, David P and Stefansson, Kari and van Duijn, Cornelia M and Hirschhorn, Joel N and Lindgren, Cecilia M and Heid, Iris M and North, Kari E and Borecki, Ingrid B and Kutalik, Zoltán and Loos, Ruth J F},
  issn         = {1553-7404},
  language     = {eng},
  number       = {10},
  publisher    = {Public Library of Science},
  series       = {PLoS Genetics},
  title        = {The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study.},
  url          = {http://dx.doi.org/10.1371/journal.pgen.1005378},
  volume       = {11},
  year         = {2015},
}