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Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits

Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% Europea... Full description

Journal Title: Justice A. E., T. W. Winkler, M. F. Feitosa, M. Graff, V. A. Fisher, K. Young, L. Barata, et al. 2017. “Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits.” Nature Communications 8 (1): 14977. doi:10.1038/ncomms14977. http://dx.doi.org/10.1038/ncomms14977.
Main Author: Justice, Anne E.
Other Authors: Winkler, Thomas W. , Feitosa, Mary F. , Graff, Misa , Fisher, Virginia A. , Young, Kristin , Barata, Llilda , Deng, Xuan , Czajkowski, Jacek , Hadley, David , Ngwa, Julius S. , Ahluwalia, Tarunveer S. , Chu, Audrey Y. , Heard-Costa, Nancy L. , Lim, Elise , Perez, Jeremiah , Eicher, John D. , Kutalik, Zoltán , Xue, Luting , Mahajan, Anubha , Renström, Frida , Wu, Joseph , Qi, Qibin , Ahmad, Shafqat , Alfred, Tamuno , Amin, Najaf , Bielak, Lawrence F. , Bonnefond, Amelie , Bragg, Jennifer , Cadby, Gemma , Chittani, Martina , Coggeshall, Scott , Corre, Tanguy , Direk, Nese , Eriksson, Joel , Fischer, Krista , Gorski, Mathias , Neergaard Harder, Marie , Horikoshi, Momoko , Huang, Tao , Huffman, Jennifer E. , Jackson, Anne U. , Justesen, Johanne Marie , Kanoni, Stavroula , Kinnunen, Leena , Kleber, Marcus E. , Komulainen, Pirjo , Kumari, Meena , Lim, Unhee , Luan, Jian'An , Lyytikäinen, Leo-Pekka , Mangino, Massimo , Manichaikul, Ani , Marten, Jonathan , Middelberg, Rita P. S. , Müller-Nurasyid, Martina , Navarro, Pau , Pérusse, Louis , Pervjakova, Natalia , Sarti, Cinzia , Smith, Albert Vernon , Smith, Jennifer A. , Stančáková, Alena , Strawbridge, Rona J. , Stringham, Heather M. , Sung, Yun Ju , Tanaka, Toshiko , Teumer, Alexander , Trompet, Stella , Van Der Laan, Sander W. , Van Der Most, Peter J. , Van Vliet-Ostaptchouk, Jana V. , Vedantam, Sailaja L. , Verweij, Niek , Vink, Jacqueline M. , Vitart, Veronique , Wu, Ying , Yengo, Loic , Zhang, Weihua , Hua Zhao, Jing , Zimmermann, Martina E. , Zubair, Niha , Abecasis, Gonçalo R. , Adair, Linda S. , Afaq, Saima , Afzal, Uzma , Bakker, Stephan J. L. , Bartz, Traci M. , Beilby, John , Bergman, Richard N. , Bergmann, Sven , Biffar, Reiner , Blangero, John , Boerwinkle, Eric , Bonnycastle, Lori L. , Bottinger, Erwin , Braga, Daniele , Buckley, Brendan M. , Buyske, Steve , Campbell, Harry , Chambers, John C. , Collins, Francis S. , Curran, Joanne E. , De Borst, Gert J. , De Craen, Anton J. M. , De Geus, Eco J. C. , Dedoussis, George , Delgado, Graciela E. , Den Ruijter, Hester M. , Eiriksdottir, Gudny , Eriksson, Anna L. , Esko, Tõnu , Faul, Jessica D. , Ford, Ian , Forrester, Terrence , Gertow, Karl , Gigante, Bruna , Glorioso, Nicola , Gong, Jian , Grallert, Harald , Grammer, Tanja B. , Grarup, Niels , Haitjema, Saskia , Hallmans, Göran , Hamsten, Anders , Hansen, Torben , Harris, Tamara B. , Hartman, Catharina A. , Hassinen, Maija , Hastie, Nicholas D. , Heath, Andrew C. , Hernandez, Dena , Hindorff, Lucia , Hocking, Lynne J. , Hollensted, Mette , Holmen, Oddgeir L. , Homuth, Georg , Jan Hottenga, Jouke , Huang, Jie , Hung, Joseph , Hutri-Kähönen, Nina , Ingelsson, Erik , James, Alan L. , Jansson, John-Olov , Jarvelin, Marjo-Riitta , Jhun, Min A. , Jørgensen, Marit E. , Juonala, Markus , Kähönen, Mika , Karlsson, Magnus , Koistinen, Heikki A. , Kolcic, Ivana , Kolovou, Genovefa , Kooperberg, Charles , Krämer, Bernhard K. , Kuusisto, Johanna , Kvaløy, Kirsti , Lakka, Timo A. , Langenberg, Claudia , Launer, Lenore J. , Leander, Karin , Lee, Nanette R. , Lind, Lars , Lindgren, Cecilia M. , Linneberg, Allan , Lobbens, Stephane , Loh, Marie , Lorentzon, Mattias , Luben, Robert , Lubke, Gitta , Ludolph-Donislawski, Anja , Lupoli, Sara , Madden, Pamela A. F. , Männikkö, Reija , Marques-Vidal, Pedro , Martin, Nicholas G. , Mckenzie, Colin A. , Mcknight, Barbara , Mellström, Dan , Menni, Cristina , Montgomery, Grant W. , Musk, Aw (Bill) , Narisu, Narisu , Nauck, Matthias , Nolte, Ilja M. , Oldehinkel, Albertine J. , Olden, Matthias , Ong, Ken K. , Padmanabhan, Sandosh , Peyser, Patricia A. , Pisinger, Charlotta , Porteous, David J. , Raitakari, Olli T. , Rankinen, Tuomo , Rao, D. C. , Rasmussen-Torvik, Laura J. , Rawal, Rajesh , Rice, Treva , Ridker, Paul M. , Rose, Lynda M. , Bien, Stephanie A. , Rudan, Igor , Sanna, Serena , Sarzynski, Mark A. , Sattar, Naveed , Savonen, Kai , Schlessinger, David , Scholtens, Salome , Schurmann, Claudia , Scott, Robert A. , Sennblad, Bengt , Siemelink, Marten A. , Silbernagel, Günther , Slagboom, P Eline , Snieder, Harold , Staessen, Jan A. , Stott, David J. , Swertz, Morris A. , Swift, Amy J. , Taylor, Kent D. , Tayo, Bamidele O. , Thorand, Barbara , Thuillier, Dorothee , Tuomilehto, Jaakko , Uitterlinden, Andre G. , Vandenput, Liesbeth , Vohl, Marie-Claude , Völzke, Henry , Vonk, Judith M. , Waeber, Gérard , Waldenberger, Melanie , Westendorp, R. G. J. , Wild, Sarah , Willemsen, Gonneke , Wolffenbuttel, Bruce H. R. , Wong, Andrew , Wright, Alan F. , Zhao, Wei , Zillikens, M Carola , Baldassarre, Damiano , Balkau, Beverley , Bandinelli, Stefania , Böger, Carsten A. , Boomsma, Dorret I. , Bouchard, Claude , Bruinenberg, Marcel , Chasman, Daniel I. , Chen, Yii-Derida , Chines, Peter S. , Cooper, Richard S.
Format: Electronic Article Electronic Article
Language: English
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ID: DOI: 10.1038/ncomms14977
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title: Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits
format: Article
creator:
  • Justice, Anne E.
  • Winkler, Thomas W.
  • Feitosa, Mary F.
  • Graff, Misa
  • Fisher, Virginia A.
  • Young, Kristin
  • Barata, Llilda
  • Deng, Xuan
  • Czajkowski, Jacek
  • Hadley, David
  • Ngwa, Julius S.
  • Ahluwalia, Tarunveer S.
  • Chu, Audrey Y.
  • Heard-Costa, Nancy L.
  • Lim, Elise
  • Perez, Jeremiah
  • Eicher, John D.
  • Kutalik, Zoltán
  • Xue, Luting
  • Mahajan, Anubha
  • Renström, Frida
  • Wu, Joseph
  • Qi, Qibin
  • Ahmad, Shafqat
  • Alfred, Tamuno
  • Amin, Najaf
  • Bielak, Lawrence F.
  • Bonnefond, Amelie
  • Bragg, Jennifer
  • Cadby, Gemma
  • Chittani, Martina
  • Coggeshall, Scott
  • Corre, Tanguy
  • Direk, Nese
  • Eriksson, Joel
  • Fischer, Krista
  • Gorski, Mathias
  • Neergaard Harder, Marie
  • Horikoshi, Momoko
  • Huang, Tao
  • Huffman, Jennifer E.
  • Jackson, Anne U.
  • Justesen, Johanne Marie
  • Kanoni, Stavroula
  • Kinnunen, Leena
  • Kleber, Marcus E.
  • Komulainen, Pirjo
  • Kumari, Meena
  • Lim, Unhee
  • Luan, Jian'An
  • Lyytikäinen, Leo-Pekka
  • Mangino, Massimo
  • Manichaikul, Ani
  • Marten, Jonathan
  • Middelberg, Rita P. S.
  • Müller-Nurasyid, Martina
  • Navarro, Pau
  • Pérusse, Louis
  • Pervjakova, Natalia
  • Sarti, Cinzia
  • Smith, Albert Vernon
  • Smith, Jennifer A.
  • Stančáková, Alena
  • Strawbridge, Rona J.
  • Stringham, Heather M.
  • Sung, Yun Ju
  • Tanaka, Toshiko
  • Teumer, Alexander
  • Trompet, Stella
  • Van Der Laan, Sander W.
  • Van Der Most, Peter J.
  • Van Vliet-Ostaptchouk, Jana V.
  • Vedantam, Sailaja L.
  • Verweij, Niek
  • Vink, Jacqueline M.
  • Vitart, Veronique
  • Wu, Ying
  • Yengo, Loic
  • Zhang, Weihua
  • Hua Zhao, Jing
  • Zimmermann, Martina E.
  • Zubair, Niha
  • Abecasis, Gonçalo R.
  • Adair, Linda S.
  • Afaq, Saima
  • Afzal, Uzma
  • Bakker, Stephan J. L.
  • Bartz, Traci M.
  • Beilby, John
  • Bergman, Richard N.
  • Bergmann, Sven
  • Biffar, Reiner
  • Blangero, John
  • Boerwinkle, Eric
  • Bonnycastle, Lori L.
  • Bottinger, Erwin
  • Braga, Daniele
  • Buckley, Brendan M.
  • Buyske, Steve
  • Campbell, Harry
  • Chambers, John C.
  • Collins, Francis S.
  • Curran, Joanne E.
  • De Borst, Gert J.
  • De Craen, Anton J. M.
  • De Geus, Eco J. C.
  • Dedoussis, George
  • Delgado, Graciela E.
  • Den Ruijter, Hester M.
  • Eiriksdottir, Gudny
  • Eriksson, Anna L.
  • Esko, Tõnu
  • Faul, Jessica D.
  • Ford, Ian
  • Forrester, Terrence
  • Gertow, Karl
  • Gigante, Bruna
  • Glorioso, Nicola
  • Gong, Jian
  • Grallert, Harald
  • Grammer, Tanja B.
  • Grarup, Niels
  • Haitjema, Saskia
  • Hallmans, Göran
  • Hamsten, Anders
  • Hansen, Torben
  • Harris, Tamara B.
  • Hartman, Catharina A.
  • Hassinen, Maija
  • Hastie, Nicholas D.
  • Heath, Andrew C.
  • Hernandez, Dena
  • Hindorff, Lucia
  • Hocking, Lynne J.
  • Hollensted, Mette
  • Holmen, Oddgeir L.
  • Homuth, Georg
  • Jan Hottenga, Jouke
  • Huang, Jie
  • Hung, Joseph
  • Hutri-Kähönen, Nina
  • Ingelsson, Erik
  • James, Alan L.
  • Jansson, John-Olov
  • Jarvelin, Marjo-Riitta
  • Jhun, Min A.
  • Jørgensen, Marit E.
  • Juonala, Markus
  • Kähönen, Mika
  • Karlsson, Magnus
  • Koistinen, Heikki A.
  • Kolcic, Ivana
  • Kolovou, Genovefa
  • Kooperberg, Charles
  • Krämer, Bernhard K.
  • Kuusisto, Johanna
  • Kvaløy, Kirsti
  • Lakka, Timo A.
  • Langenberg, Claudia
  • Launer, Lenore J.
  • Leander, Karin
  • Lee, Nanette R.
  • Lind, Lars
  • Lindgren, Cecilia M.
  • Linneberg, Allan
  • Lobbens, Stephane
  • Loh, Marie
  • Lorentzon, Mattias
  • Luben, Robert
  • Lubke, Gitta
  • Ludolph-Donislawski, Anja
  • Lupoli, Sara
  • Madden, Pamela A. F.
  • Männikkö, Reija
  • Marques-Vidal, Pedro
  • Martin, Nicholas G.
  • Mckenzie, Colin A.
  • Mcknight, Barbara
  • Mellström, Dan
  • Menni, Cristina
  • Montgomery, Grant W.
  • Musk, Aw (Bill)
  • Narisu, Narisu
  • Nauck, Matthias
  • Nolte, Ilja M.
  • Oldehinkel, Albertine J.
  • Olden, Matthias
  • Ong, Ken K.
  • Padmanabhan, Sandosh
  • Peyser, Patricia A.
  • Pisinger, Charlotta
  • Porteous, David J.
  • Raitakari, Olli T.
  • Rankinen, Tuomo
  • Rao, D. C.
  • Rasmussen-Torvik, Laura J.
  • Rawal, Rajesh
  • Rice, Treva
  • Ridker, Paul M.
  • Rose, Lynda M.
  • Bien, Stephanie A.
  • Rudan, Igor
  • Sanna, Serena
  • Sarzynski, Mark A.
  • Sattar, Naveed
  • Savonen, Kai
  • Schlessinger, David
  • Scholtens, Salome
  • Schurmann, Claudia
  • Scott, Robert A.
  • Sennblad, Bengt
  • Siemelink, Marten A.
  • Silbernagel, Günther
  • Slagboom, P Eline
  • Snieder, Harold
  • Staessen, Jan A.
  • Stott, David J.
  • Swertz, Morris A.
  • Swift, Amy J.
  • Taylor, Kent D.
  • Tayo, Bamidele O.
  • Thorand, Barbara
  • Thuillier, Dorothee
  • Tuomilehto, Jaakko
  • Uitterlinden, Andre G.
  • Vandenput, Liesbeth
  • Vohl, Marie-Claude
  • Völzke, Henry
  • Vonk, Judith M.
  • Waeber, Gérard
  • Waldenberger, Melanie
  • Westendorp, R. G. J.
  • Wild, Sarah
  • Willemsen, Gonneke
  • Wolffenbuttel, Bruce H. R.
  • Wong, Andrew
  • Wright, Alan F.
  • Zhao, Wei
  • Zillikens, M Carola
  • Baldassarre, Damiano
  • Balkau, Beverley
  • Bandinelli, Stefania
  • Böger, Carsten A.
  • Boomsma, Dorret I.
  • Bouchard, Claude
  • Bruinenberg, Marcel
  • Chasman, Daniel I.
  • Chen, Yii-Derida
  • Chines, Peter S.
  • Cooper, Richard S.
subjects:
  • Article
ispartof: Justice, A. E., T. W. Winkler, M. F. Feitosa, M. Graff, V. A. Fisher, K. Young, L. Barata, et al. 2017. “Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits.” Nature Communications 8 (1): 14977. doi:10.1038/ncomms14977. http://dx.doi.org/10.1038/ncomms14977.
description: Few genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.
language: eng
source:
identifier: DOI: 10.1038/ncomms14977
fulltext: fulltext_linktorsrc
url: Link


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titleGenome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits
creatorJustice, Anne E. ; Winkler, Thomas W. ; Feitosa, Mary F. ; Graff, Misa ; Fisher, Virginia A. ; Young, Kristin ; Barata, Llilda ; Deng, Xuan ; Czajkowski, Jacek ; Hadley, David ; Ngwa, Julius S. ; Ahluwalia, Tarunveer S. ; Chu, Audrey Y. ; Heard-Costa, Nancy L. ; Lim, Elise ; Perez, Jeremiah ; Eicher, John D. ; Kutalik, Zoltán ; Xue, Luting ; Mahajan, Anubha ; Renström, Frida ; Wu, Joseph ; Qi, Qibin ; Ahmad, Shafqat ; Alfred, Tamuno ; Amin, Najaf ; Bielak, Lawrence F. ; Bonnefond, Amelie ; Bragg, Jennifer ; Cadby, Gemma ; Chittani, Martina ; Coggeshall, Scott ; Corre, Tanguy ; Direk, Nese ; Eriksson, Joel ; Fischer, Krista ; Gorski, Mathias ; Neergaard Harder, Marie ; Horikoshi, Momoko ; Huang, Tao ; Huffman, Jennifer E. ; Jackson, Anne U. ; Justesen, Johanne Marie ; Kanoni, Stavroula ; Kinnunen, Leena ; Kleber, Marcus E. ; Komulainen, Pirjo ; Kumari, Meena ; Lim, Unhee ; Luan, Jian'An ; Lyytikäinen, Leo-Pekka ; Mangino, Massimo ; Manichaikul, Ani ; Marten, Jonathan ; Middelberg, Rita P. S. ; Müller-Nurasyid, Martina ; Navarro, Pau ; Pérusse, Louis ; Pervjakova, Natalia ; Sarti, Cinzia ; Smith, Albert Vernon ; Smith, Jennifer A. ; Stančáková, Alena ; Strawbridge, Rona J. ; Stringham, Heather M. ; Sung, Yun Ju ; Tanaka, Toshiko ; Teumer, Alexander ; Trompet, Stella ; Van Der Laan, Sander W. ; Van Der Most, Peter J. ; Van Vliet-Ostaptchouk, Jana V. ; Vedantam, Sailaja L. ; Verweij, Niek ; Vink, Jacqueline M. ; Vitart, Veronique ; Wu, Ying ; Yengo, Loic ; Zhang, Weihua ; Hua Zhao, Jing ; Zimmermann, Martina E. ; Zubair, Niha ; Abecasis, Gonçalo R. ; Adair, Linda S. ; Afaq, Saima ; Afzal, Uzma ; Bakker, Stephan J. L. ; Bartz, Traci M. ; Beilby, John ; Bergman, Richard N. ; Bergmann, Sven ; Biffar, Reiner ; Blangero, John ; Boerwinkle, Eric ; Bonnycastle, Lori L. ; Bottinger, Erwin ; Braga, Daniele ; Buckley, Brendan M. ; Buyske, Steve ; Campbell, Harry ; Chambers, John C. ; Collins, Francis S. ; Curran, Joanne E. ; De Borst, Gert J. ; De Craen, Anton J. M. ; De Geus, Eco J. C. ; Dedoussis, George ; Delgado, Graciela E. ; Den Ruijter, Hester M. ; Eiriksdottir, Gudny ; Eriksson, Anna L. ; Esko, Tõnu ; Faul, Jessica D. ; Ford, Ian ; Forrester, Terrence ; Gertow, Karl ; Gigante, Bruna ; Glorioso, Nicola ; Gong, Jian ; Grallert, Harald ; Grammer, Tanja B. ; Grarup, Niels ; Haitjema, Saskia ; Hallmans, Göran ; Hamsten, Anders ; Hansen, Torben ; Harris, Tamara B. ; Hartman, Catharina A. ; Hassinen, Maija ; Hastie, Nicholas D. ; Heath, Andrew C. ; Hernandez, Dena ; Hindorff, Lucia ; Hocking, Lynne J. ; Hollensted, Mette ; Holmen, Oddgeir L. ; Homuth, Georg ; Jan Hottenga, Jouke ; Huang, Jie ; Hung, Joseph ; Hutri-Kähönen, Nina ; Ingelsson, Erik ; James, Alan L. ; Jansson, John-Olov ; Jarvelin, Marjo-Riitta ; Jhun, Min A. ; Jørgensen, Marit E. ; Juonala, Markus ; Kähönen, Mika ; Karlsson, Magnus ; Koistinen, Heikki A. ; Kolcic, Ivana ; Kolovou, Genovefa ; Kooperberg, Charles ; Krämer, Bernhard K. ; Kuusisto, Johanna ; Kvaløy, Kirsti ; Lakka, Timo A. ; Langenberg, Claudia ; Launer, Lenore J. ; Leander, Karin ; Lee, Nanette R. ; Lind, Lars ; Lindgren, Cecilia M. ; Linneberg, Allan ; Lobbens, Stephane ; Loh, Marie ; Lorentzon, Mattias ; Luben, Robert ; Lubke, Gitta ; Ludolph-Donislawski, Anja ; Lupoli, Sara ; Madden, Pamela A. F. ; Männikkö, Reija ; Marques-Vidal, Pedro ; Martin, Nicholas G. ; Mckenzie, Colin A. ; Mcknight, Barbara ; Mellström, Dan ; Menni, Cristina ; Montgomery, Grant W. ; Musk, Aw (Bill) ; Narisu, Narisu ; Nauck, Matthias ; Nolte, Ilja M. ; Oldehinkel, Albertine J. ; Olden, Matthias ; Ong, Ken K. ; Padmanabhan, Sandosh ; Peyser, Patricia A. ; Pisinger, Charlotta ; Porteous, David J. ; Raitakari, Olli T. ; Rankinen, Tuomo ; Rao, D. C. ; Rasmussen-Torvik, Laura J. ; Rawal, Rajesh ; Rice, Treva ; Ridker, Paul M. ; Rose, Lynda M. ; Bien, Stephanie A. ; Rudan, Igor ; Sanna, Serena ; Sarzynski, Mark A. ; Sattar, Naveed ; Savonen, Kai ; Schlessinger, David ; Scholtens, Salome ; Schurmann, Claudia ; Scott, Robert A. ; Sennblad, Bengt ; Siemelink, Marten A. ; Silbernagel, Günther ; Slagboom, P Eline ; Snieder, Harold ; Staessen, Jan A. ; Stott, David J. ; Swertz, Morris A. ; Swift, Amy J. ; Taylor, Kent D. ; Tayo, Bamidele O. ; Thorand, Barbara ; Thuillier, Dorothee ; Tuomilehto, Jaakko ; Uitterlinden, Andre G. ; Vandenput, Liesbeth ; Vohl, Marie-Claude ; Völzke, Henry ; Vonk, Judith M. ; Waeber, Gérard ; Waldenberger, Melanie ; Westendorp, R. G. J. ; Wild, Sarah ; Willemsen, Gonneke ; Wolffenbuttel, Bruce H. R. ; Wong, Andrew ; Wright, Alan F. ; Zhao, Wei ; Zillikens, M Carola ; Baldassarre, Damiano ; Balkau, Beverley ; Bandinelli, Stefania ; Böger, Carsten A. ; Boomsma, Dorret I. ; Bouchard, Claude ; Bruinenberg, Marcel ; Chasman, Daniel I. ; Chen, Yii-Derida ; Chines, Peter S. ; Cooper, Richard S.
ispartofJustice, A. E., T. W. Winkler, M. F. Feitosa, M. Graff, V. A. Fisher, K. Young, L. Barata, et al. 2017. “Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits.” Nature Communications 8 (1): 14977. doi:10.1038/ncomms14977. http://dx.doi.org/10.1038/ncomms14977.
identifierDOI: 10.1038/ncomms14977
descriptionFew genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.
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0Justice, Anne E.
1Winkler, Thomas W.
2Feitosa, Mary F.
3Graff, Misa
4Fisher, Virginia A.
5Young, Kristin
6Barata, Llilda
7Deng, Xuan
8Czajkowski, Jacek
9Hadley, David
10Ngwa, Julius S.
11Ahluwalia, Tarunveer S.
12Chu, Audrey Y.
13Heard-Costa, Nancy L.
14Lim, Elise
15Perez, Jeremiah
16Eicher, John D.
17Kutalik, Zoltán
18Xue, Luting
19Mahajan, Anubha
20Renström, Frida
21Wu, Joseph
22Qi, Qibin
23Ahmad, Shafqat
24Alfred, Tamuno
25Amin, Najaf
26Bielak, Lawrence F.
27Bonnefond, Amelie
28Bragg, Jennifer
29Cadby, Gemma
30Chittani, Martina
31Coggeshall, Scott
32Corre, Tanguy
33Direk, Nese
34Eriksson, Joel
35Fischer, Krista
36Gorski, Mathias
37Neergaard Harder, Marie
38Horikoshi, Momoko
39Huang, Tao
40Huffman, Jennifer E.
41Jackson, Anne U.
42Justesen, Johanne Marie
43Kanoni, Stavroula
44Kinnunen, Leena
45Kleber, Marcus E.
46Komulainen, Pirjo
47Kumari, Meena
48Lim, Unhee
49Luan, Jian'an
50Lyytikäinen, Leo-Pekka
51Mangino, Massimo
52Manichaikul, Ani
53Marten, Jonathan
54Middelberg, Rita P. S.
55Müller-Nurasyid, Martina
56Navarro, Pau
57Pérusse, Louis
58Pervjakova, Natalia
59Sarti, Cinzia
60Smith, Albert Vernon
61Smith, Jennifer A.
62Stančáková, Alena
63Strawbridge, Rona J.
64Stringham, Heather M.
65Sung, Yun Ju
66Tanaka, Toshiko
67Teumer, Alexander
68Trompet, Stella
69van der Laan, Sander W.
70van der Most, Peter J.
71Van Vliet-Ostaptchouk, Jana V.
72Vedantam, Sailaja L.
73Verweij, Niek
74Vink, Jacqueline M.
75Vitart, Veronique
76Wu, Ying
77Yengo, Loic
78Zhang, Weihua
79Hua Zhao, Jing
80Zimmermann, Martina E.
81Zubair, Niha
82Abecasis, Gonçalo R.
83Adair, Linda S.
84Afaq, Saima
85Afzal, Uzma
86Bakker, Stephan J. L.
87Bartz, Traci M.
88Beilby, John
89Bergman, Richard N.
90Bergmann, Sven
91Biffar, Reiner
92Blangero, John
93Boerwinkle, Eric
94Bonnycastle, Lori L.
95Bottinger, Erwin
96Braga, Daniele
97Buckley, Brendan M.
98Buyske, Steve
99Campbell, Harry
100...
titleGenome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits
descriptionFew genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.
general
0Digital Access to Scholarship at Harvard (DASH)
1Nature Publishing Group
2English
310.1038/ncomms14977
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titleGenome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits
authorJustice, Anne E. ; Winkler, Thomas W. ; Feitosa, Mary F. ; Graff, Misa ; Fisher, Virginia A. ; Young, Kristin ; Barata, Llilda ; Deng, Xuan ; Czajkowski, Jacek ; Hadley, David ; Ngwa, Julius S. ; Ahluwalia, Tarunveer S. ; Chu, Audrey Y. ; Heard-Costa, Nancy L. ; Lim, Elise ; Perez, Jeremiah ; Eicher, John D. ; Kutalik, Zoltán ; Xue, Luting ; Mahajan, Anubha ; Renström, Frida ; Wu, Joseph ; Qi, Qibin ; Ahmad, Shafqat ; Alfred, Tamuno ; Amin, Najaf ; Bielak, Lawrence F. ; Bonnefond, Amelie ; Bragg, Jennifer ; Cadby, Gemma ; Chittani, Martina ; Coggeshall, Scott ; Corre, Tanguy ; Direk, Nese ; Eriksson, Joel ; Fischer, Krista ; Gorski, Mathias ; Neergaard Harder, Marie ; Horikoshi, Momoko ; Huang, Tao ; Huffman, Jennifer E. ; Jackson, Anne U. ; Justesen, Johanne Marie ; Kanoni, Stavroula ; Kinnunen, Leena ; Kleber, Marcus E. ; Komulainen, Pirjo ; Kumari, Meena ; Lim, Unhee ; Luan, Jian'An ; Lyytikäinen, Leo-Pekka ; Mangino, Massimo ; Manichaikul, Ani ; Marten, Jonathan ; Middelberg, Rita P. S. ; Müller-Nurasyid, Martina ; Navarro, Pau ; Pérusse, Louis ; Pervjakova, Natalia ; Sarti, Cinzia ; Smith, Albert Vernon ; Smith, Jennifer A. ; Stančáková, Alena ; Strawbridge, Rona J. ; Stringham, Heather M. ; Sung, Yun Ju ; Tanaka, Toshiko ; Teumer, Alexander ; Trompet, Stella ; Van Der Laan, Sander W. ; Van Der Most, Peter J. ; Van Vliet-Ostaptchouk, Jana V. ; Vedantam, Sailaja L. ; Verweij, Niek ; Vink, Jacqueline M. ; Vitart, Veronique ; Wu, Ying ; Yengo, Loic ; Zhang, Weihua ; Hua Zhao, Jing ; Zimmermann, Martina E. ; Zubair, Niha ; Abecasis, Gonçalo R. ; Adair, Linda S. ; Afaq, Saima ; Afzal, Uzma ; Bakker, Stephan J. L. ; Bartz, Traci M. ; Beilby, John ; Bergman, Richard N. ; Bergmann, Sven ; Biffar, Reiner ; Blangero, John ; Boerwinkle, Eric ; Bonnycastle, Lori L. ; Bottinger, Erwin ; Braga, Daniele ; Buckley, Brendan M. ; Buyske, Steve ; Campbell, Harry ; Chambers, John C. ; Collins, Francis S. ; Curran, Joanne E. ; De Borst, Gert J. ; De Craen, Anton J. M. ; De Geus, Eco J. C. ; Dedoussis, George ; Delgado, Graciela E. ; Den Ruijter, Hester M. ; Eiriksdottir, Gudny ; Eriksson, Anna L. ; Esko, Tõnu ; Faul, Jessica D. ; Ford, Ian ; Forrester, Terrence ; Gertow, Karl ; Gigante, Bruna ; Glorioso, Nicola ; Gong, Jian ; Grallert, Harald ; Grammer, Tanja B. ; Grarup, Niels ; Haitjema, Saskia ; Hallmans, Göran ; Hamsten, Anders ; Hansen, Torben ; Harris, Tamara B. ; Hartman, Catharina A. ; Hassinen, Maija ; Hastie, Nicholas D. ; Heath, Andrew C. ; Hernandez, Dena ; Hindorff, Lucia ; Hocking, Lynne J. ; Hollensted, Mette ; Holmen, Oddgeir L. ; Homuth, Georg ; Jan Hottenga, Jouke ; Huang, Jie ; Hung, Joseph ; Hutri-Kähönen, Nina ; Ingelsson, Erik ; James, Alan L. ; Jansson, John-Olov ; Jarvelin, Marjo-Riitta ; Jhun, Min A. ; Jørgensen, Marit E. ; Juonala, Markus ; Kähönen, Mika ; Karlsson, Magnus ; Koistinen, Heikki A. ; Kolcic, Ivana ; Kolovou, Genovefa ; Kooperberg, Charles ; Krämer, Bernhard K. ; Kuusisto, Johanna ; Kvaløy, Kirsti ; Lakka, Timo A. ; Langenberg, Claudia ; Launer, Lenore J. ; Leander, Karin ; Lee, Nanette R. ; Lind, Lars ; Lindgren, Cecilia M. ; Linneberg, Allan ; Lobbens, Stephane ; Loh, Marie ; Lorentzon, Mattias ; Luben, Robert ; Lubke, Gitta ; Ludolph-Donislawski, Anja ; Lupoli, Sara ; Madden, Pamela A. F. ; Männikkö, Reija ; Marques-Vidal, Pedro ; Martin, Nicholas G. ; Mckenzie, Colin A. ; Mcknight, Barbara ; Mellström, Dan ; Menni, Cristina ; Montgomery, Grant W. ; Musk, Aw (Bill) ; Narisu, Narisu ; Nauck, Matthias ; Nolte, Ilja M. ; Oldehinkel, Albertine J. ; Olden, Matthias ; Ong, Ken K. ; Padmanabhan, Sandosh ; Peyser, Patricia A. ; Pisinger, Charlotta ; Porteous, David J. ; Raitakari, Olli T. ; Rankinen, Tuomo ; Rao, D. C. ; Rasmussen-Torvik, Laura J. ; Rawal, Rajesh ; Rice, Treva ; Ridker, Paul M. ; Rose, Lynda M. ; Bien, Stephanie A. ; Rudan, Igor ; Sanna, Serena ; Sarzynski, Mark A. ; Sattar, Naveed ; Savonen, Kai ; Schlessinger, David ; Scholtens, Salome ; Schurmann, Claudia ; Scott, Robert A. ; Sennblad, Bengt ; Siemelink, Marten A. ; Silbernagel, Günther ; Slagboom, P Eline ; Snieder, Harold ; Staessen, Jan A. ; Stott, David J. ; Swertz, Morris A. ; Swift, Amy J. ; Taylor, Kent D. ; Tayo, Bamidele O. ; Thorand, Barbara ; Thuillier, Dorothee ; Tuomilehto, Jaakko ; Uitterlinden, Andre G. ; Vandenput, Liesbeth ; Vohl, Marie-Claude ; Völzke, Henry ; Vonk, Judith M. ; Waeber, Gérard ; Waldenberger, Melanie ; Westendorp, R. G. J. ; Wild, Sarah ; Willemsen, Gonneke ; Wolffenbuttel, Bruce H. R. ; Wong, Andrew ; Wright, Alan F. ; Zhao, Wei ; Zillikens, M Carola ; Baldassarre, Damiano ; Balkau, Beverley ; Bandinelli, Stefania ; Böger, Carsten A. ; Boomsma, Dorret I. ; Bouchard, Claude ; Bruinenberg, Marcel ; Chasman, Daniel I. ; Chen, Yii-Derida ; Chines, Peter S. ; Cooper, Richard S.
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0Justice, Anne E
1Winkler, Thomas W
2Feitosa, Mary F
3Graff, Misa
4Fisher, Virginia A
5Young, Kristin
6Barata, Llilda
7Deng, Xuan
8Czajkowski, Jacek
9Hadley, David
10Ngwa, Julius S
11Ahluwalia, Tarunveer S
12Chu, Audrey Y
13Heard-Costa, Nancy L
14Lim, Elise
15Perez, Jeremiah
16Eicher, John D
17Kutalik, Zoltán
18Xue, Luting
19Mahajan, Anubha
20Renström, Frida
21Wu, Joseph
22Qi, Qibin
23Ahmad, Shafqat
24Alfred, Tamuno
25Amin, Najaf
26Bielak, Lawrence F
27Bonnefond, Amelie
28Bragg, Jennifer
29Cadby, Gemma
30Chittani, Martina
31Coggeshall, Scott
32Corre, Tanguy
33Direk, Nese
34Eriksson, Joel
35Fischer, Krista
36Gorski, Mathias
37Neergaard Harder, Marie
38Horikoshi, Momoko
39Huang, Tao
40Huffman, Jennifer E
41Jackson, Anne U
42Justesen, Johanne Marie
43Kanoni, Stavroula
44Kinnunen, Leena
45Kleber, Marcus E
46Komulainen, Pirjo
47Kumari, Meena
48Lim, Unhee
49Luan, Jian'an
50Lyytikäinen, Leo-Pekka
51Mangino, Massimo
52Manichaikul, Ani
53Marten, Jonathan
54Middelberg, Rita P. S
55Müller-Nurasyid, Martina
56Navarro, Pau
57Pérusse, Louis
58Pervjakova, Natalia
59Sarti, Cinzia
60Smith, Albert Vernon
61Smith, Jennifer A
62Stančáková, Alena
63Strawbridge, Rona J
64Stringham, Heather M
65Sung, Yun Ju
66Tanaka, Toshiko
67Teumer, Alexander
68Trompet, Stella
69van der Laan, Sander W
70van der Most, Peter J
71Van Vliet-Ostaptchouk, Jana V
72Vedantam, Sailaja L
73Verweij, Niek
74Vink, Jacqueline M
75Vitart, Veronique
76Wu, Ying
77Yengo, Loic
78Zhang, Weihua
79Hua Zhao, Jing
80Zimmermann, Martina E
81Zubair, Niha
82Abecasis, Gonçalo R
83Adair, Linda S
84Afaq, Saima
85Afzal, Uzma
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93Boerwinkle, Eric
94Bonnycastle, Lori L
95Bottinger, Erwin
96Braga, Daniele
97Buckley, Brendan M
98Buyske, Steve
99Campbell, Harry
100...
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12Audrey Y.
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40Jennifer E.
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59Albert Vernon
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62Rona J.
63Heather M.
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68Sander W.
69Peter J.
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71Sailaja L.
72Niek
73Jacqueline M.
74Veronique
75Ying
76Loic
77Weihua
78Jing
79Martina E.
80Niha
81Gonçalo R.
82Linda S.
83Saima
84Uzma
85Stephan J. L.
86Traci M.
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88Richard N.
89Sven
90Reiner
91Eric
92Lori L.
93Erwin
94Daniele
95Brendan M.
96Steve
97Harry
98John C.
99Francis S.
100...
au
0Justice, Anne E.
1Winkler, Thomas W.
2Feitosa, Mary F.
3Graff, Misa
4Fisher, Virginia A.
5Young, Kristin
6Barata, Llilda
7Deng, Xuan
8Czajkowski, Jacek
9Hadley, David
10Ngwa, Julius S.
11Ahluwalia, Tarunveer S.
12Chu, Audrey Y.
13Heard-Costa, Nancy L.
14Lim, Elise
15Perez, Jeremiah
16Eicher, John D.
17Kutalik, Zoltán
18Xue, Luting
19Mahajan, Anubha
20Renström, Frida
21Wu, Joseph
22Qi, Qibin
23Ahmad, Shafqat
24Alfred, Tamuno
25Amin, Najaf
26Bielak, Lawrence F.
27Bonnefond, Amelie
28Bragg, Jennifer
29Cadby, Gemma
30Chittani, Martina
31Coggeshall, Scott
32Corre, Tanguy
33Direk, Nese
34Eriksson, Joel
35Fischer, Krista
36Gorski, Mathias
37Neergaard Harder, Marie
38Horikoshi, Momoko
39Huang, Tao
40Huffman, Jennifer E.
41Jackson, Anne U.
42Justesen, Johanne Marie
43Kanoni, Stavroula
44Kinnunen, Leena
45Kleber, Marcus E.
46Komulainen, Pirjo
47Kumari, Meena
48Lim, Unhee
49Luan, Jian'an
50Lyytikäinen, Leo-Pekka
51Mangino, Massimo
52Manichaikul, Ani
53Marten, Jonathan
54Middelberg, Rita P. S.
55Müller-Nurasyid, Martina
56Navarro, Pau
57Pérusse, Louis
58Pervjakova, Natalia
59Sarti, Cinzia
60Smith, Albert Vernon
61Smith, Jennifer A.
62Stančáková, Alena
63Strawbridge, Rona J.
64Stringham, Heather M.
65Sung, Yun Ju
66Tanaka, Toshiko
67Teumer, Alexander
68Trompet, Stella
69van der Laan, Sander W.
70van der Most, Peter J.
71Van Vliet-Ostaptchouk, Jana V.
72Vedantam, Sailaja L.
73Verweij, Niek
74Vink, Jacqueline M.
75Vitart, Veronique
76Wu, Ying
77Yengo, Loic
78Zhang, Weihua
79Hua Zhao, Jing
80Zimmermann, Martina E.
81Zubair, Niha
82Abecasis, Gonçalo R.
83Adair, Linda S.
84Afaq, Saima
85Afzal, Uzma
86Bakker, Stephan J. L.
87Bartz, Traci M.
88Beilby, John
89Bergman, Richard N.
90Bergmann, Sven
91Biffar, Reiner
92Blangero, John
93Boerwinkle, Eric
94Bonnycastle, Lori L.
95Bottinger, Erwin
96Braga, Daniele
97Buckley, Brendan M.
98Buyske, Steve
99Campbell, Harry
100...
atitleGenome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits
jtitleNature Communications
date2017
risdate2017
genrearticle
ristypeJOUR
abstractFew genome-wide association studies (GWAS) account for environmental exposures, like smoking, potentially impacting the overall trait variance when investigating the genetic contribution to obesity-related traits. Here, we use GWAS data from 51,080 current smokers and 190,178 nonsmokers (87% European descent) to identify loci influencing BMI and central adiposity, measured as waist circumference and waist-to-hip ratio both adjusted for BMI. We identify 23 novel genetic loci, and 9 loci with convincing evidence of gene-smoking interaction (GxSMK) on obesity-related traits. We show consistent direction of effect for all identified loci and significance for 18 novel and for 5 interaction loci in an independent study sample. These loci highlight novel biological functions, including response to oxidative stress, addictive behaviour, and regulatory functions emphasizing the importance of accounting for environment in genetic analyses. Our results suggest that tobacco smoking may alter the genetic susceptibility to overall adiposity and body fat distribution.
pubNature Publishing Group
doi10.1038/ncomms14977
urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC5414044/pdf/
pages14977
orcididdiva-portal.org=authority-person:63373
volume8
issn20411723
isbn0004000646000
eissn20411723
oafree_for_read