Abstract
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.
Originalsprog | Engelsk |
---|---|
Artikelnummer | 14977 |
Tidsskrift | Nature Communications |
Vol/bind | 8 |
Antal sider | 19 |
ISSN | 2041-1723 |
DOI | |
Status | Udgivet - 26 apr. 2017 |
Citationsformater
- APA
- Standard
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- Vancouver
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- BIBTEX
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Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits. / Justice, Anne E; Winkler, Thomas W; Feitosa, Mary F; Graff, Misa; Fisher, Virginia A; Young, Kristin L; Barata, Llilda; Deng, Xuan; Czajkowski, Jacek; Hadley, David; Ngwa, Julius S; Ahluwalia, Tarunveer Singh; Chu, Audrey Y; Heard-Costa, Nancy L; Lim, Elise; Perez, Jeremiah; Eicher, John D; Kutalik, Zoltan; Xue, Luting; Mahajan, Anubha; Renström, Frida; Wu, Joseph C; Qi, Qibin; Ahmad, Shafqat; Alfred, Tamuno; Amin, Najaf; Bielak, Lawrence F; Bonnefond, Amélie; Bragg-Gresham, Jennifer L; Cadby, Gemma; Chittani, Martina; Coggeshall, Scott; Corre, Tanguy; Direk, Nese; Eriksson, Joel; Fischer, Krista; Gorski, Mathias; Neergaard Harder, Marie; Horikoshi, Momoko; Huang, Tao-wei; 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, Goncalo 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 P; Braga, Daniele; Buckley, Brendan M; Buyske, Steve; Campbell, Harry; Chambers, John C; Collins, Francis S; Curran, Joanne E; de Borst, Gert Jan; 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 A; 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, Stéphane; 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, Dabeeru C; Rasmussen-Torvik, Laura J; Rawal, Rajesh; Rice, Treva K; 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, Gerard; 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; Cucca, Francesco; Cusi, Daniele; Faire, Ulf de; Ferrucci, Luigi; Franks, Paul W; Froguel, Philippe; Gordon-Larsen, Penny; Grabe, Hans Jörgen; Gudnason, Vilmundur; Haiman, Christopher A; Hayward, Caroline; Hveem, Kristian; Johnson, Andrew D; Wouter Jukema, J; Kardia, Sharon L R; Kivimaki, Mika; Kooner, Jaspal S; Kuh, Diana; Laakso, Markku; Lehtimäki, Terho; Marchand, Loic Le; März, Winfried; McCarthy, Mark I; Metspalu, Andres; Morris, Andrew P; Ohlsson, Claes; Palmer, Lyle J; Pasterkamp, Gerard; Pedersen, Oluf; Peters, Annette; Peters, Ulrike; Polasek, Ozren; Psaty, Bruce M; Qi, Lu; Rauramaa, Rainer; Smith, Blair H; Sørensen, Thorkild I A; Strauch, Konstantin; Tiemeier, Henning; Tremoli, Elena; van der Harst, Pim; Vestergaard, Henrik; Vollenweider, Peter; Wareham, Nicholas J; Weir, David R; Whitfield, John B; Wilson, James F; Tyrrell, Jessica; Frayling, Timothy M; Barroso, Inês; Boehnke, Michael; Deloukas, Panagiotis; Fox, Caroline S; Hirschhorn, Joel N; Hunter, David J; Spector, Tim D; Strachan, David P; van Duijn, Cornélia M; Heid, Iris M; Mohlke, Karen L; Marchini, Jonathan L; Loos, Ruth J F; Kilpeläinen, Tuomas O; Liu, Ching-Ti; Borecki, Ingrid B; North, Kari E; Cupples, L Adrienne.
I: Nature Communications, Bind 8, 14977, 26.04.2017.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
}
TY - JOUR
T1 - Genome-wide meta-analysis of 241,258 adults accounting for smoking behaviour identifies novel loci for obesity traits
AU - Justice, Anne E
AU - Winkler, Thomas W
AU - Feitosa, Mary F
AU - Graff, Misa
AU - Fisher, Virginia A
AU - Young, Kristin L
AU - Barata, Llilda
AU - Deng, Xuan
AU - Czajkowski, Jacek
AU - Hadley, David
AU - Ngwa, Julius S
AU - Ahluwalia, Tarunveer Singh
AU - Chu, Audrey Y
AU - Heard-Costa, Nancy L
AU - Lim, Elise
AU - Perez, Jeremiah
AU - Eicher, John D
AU - Kutalik, Zoltan
AU - Xue, Luting
AU - Mahajan, Anubha
AU - Renström, Frida
AU - Wu, Joseph C
AU - Qi, Qibin
AU - Ahmad, Shafqat
AU - Alfred, Tamuno
AU - Amin, Najaf
AU - Bielak, Lawrence F
AU - Bonnefond, Amélie
AU - Bragg-Gresham, Jennifer L
AU - Cadby, Gemma
AU - Chittani, Martina
AU - Coggeshall, Scott
AU - Corre, Tanguy
AU - Direk, Nese
AU - Eriksson, Joel
AU - Fischer, Krista
AU - Gorski, Mathias
AU - Neergaard Harder, Marie
AU - Horikoshi, Momoko
AU - Huang, Tao-wei
AU - Huffman, Jennifer E
AU - Jackson, Anne U
AU - Justesen, Johanne Marie
AU - Kanoni, Stavroula
AU - Kinnunen, Leena
AU - Kleber, Marcus E
AU - Komulainen, Pirjo
AU - Kumari, Meena
AU - Lim, Unhee
AU - Luan, Jian'an
AU - Lyytikäinen, Leo-Pekka
AU - Mangino, Massimo
AU - Manichaikul, Ani
AU - Marten, Jonathan
AU - Middelberg, Rita P S
AU - Müller-Nurasyid, Martina
AU - Navarro, Pau
AU - Pérusse, Louis
AU - Pervjakova, Natalia
AU - Sarti, Cinzia
AU - Smith, Albert Vernon
AU - Smith, Jennifer A
AU - Stančáková, Alena
AU - Strawbridge, Rona J
AU - Stringham, Heather M
AU - Sung, Yun Ju
AU - Tanaka, Toshiko
AU - Teumer, Alexander
AU - Trompet, Stella
AU - van der Laan, Sander W
AU - van der Most, Peter J
AU - van Vliet-Ostaptchouk, Jana V
AU - Vedantam, Sailaja L
AU - Verweij, Niek
AU - Vink, Jacqueline M
AU - Vitart, Veronique
AU - Wu, Ying
AU - Yengo, Loic
AU - Zhang, Weihua
AU - Hua Zhao, Jing
AU - Zimmermann, Martina E
AU - Zubair, Niha
AU - Abecasis, Goncalo R
AU - Adair, Linda S
AU - Afaq, Saima
AU - Afzal, Uzma
AU - Bakker, Stephan J L
AU - Bartz, Traci M
AU - Beilby, John
AU - Bergman, Richard N
AU - Bergmann, Sven
AU - Biffar, Reiner
AU - Blangero, John
AU - Boerwinkle, Eric
AU - Bonnycastle, Lori L
AU - Bottinger, Erwin P
AU - Braga, Daniele
AU - Buckley, Brendan M
AU - Buyske, Steve
AU - Campbell, Harry
AU - Chambers, John C
AU - Collins, Francis S
AU - Curran, Joanne E
AU - de Borst, Gert Jan
AU - De Craen, Anton J M
AU - de Geus, Eco J C
AU - Dedoussis, George
AU - Delgado, Graciela E
AU - den Ruijter, Hester M
AU - Eiriksdottir, Gudny
AU - Eriksson, Anna L
AU - Esko, Tõnu
AU - Faul, Jessica D
AU - Ford, Ian
AU - Forrester, Terrence
AU - Gertow, Karl
AU - Gigante, Bruna
AU - Glorioso, Nicola
AU - Gong, Jian
AU - Grallert, Harald
AU - Grammer, Tanja B
AU - Grarup, Niels
AU - Haitjema, Saskia
AU - Hallmans, Göran
AU - Hamsten, Anders
AU - Hansen, Torben
AU - Harris, Tamara B
AU - Hartman, Catharina A
AU - Hassinen, Maija
AU - Hastie, Nicholas D
AU - Heath, Andrew C
AU - Hernandez, Dena
AU - Hindorff, Lucia A
AU - Hocking, Lynne J
AU - Hollensted, Mette
AU - Holmen, Oddgeir L
AU - Homuth, Georg
AU - Jan Hottenga, Jouke
AU - Huang, Jie
AU - Hung, Joseph
AU - Hutri-Kähönen, Nina
AU - Ingelsson, Erik
AU - James, Alan L
AU - Jansson, John-Olov
AU - Jarvelin, Marjo Riitta
AU - Jhun, Min A
AU - Jørgensen, Marit E
AU - Juonala, Markus
AU - Kähönen, Mika
AU - Karlsson, Magnus
AU - Koistinen, Heikki A
AU - Kolcic, Ivana
AU - Kolovou, Genovefa
AU - Kooperberg, Charles
AU - Krämer, Bernhard K
AU - Kuusisto, Johanna
AU - Kvaløy, Kirsti
AU - Lakka, Timo A
AU - Langenberg, Claudia
AU - Launer, Lenore J
AU - Leander, Karin
AU - Lee, Nanette R
AU - Lind, Lars
AU - Lindgren, Cecilia M
AU - Linneberg, Allan
AU - Lobbens, Stéphane
AU - Loh, Marie
AU - Lorentzon, Mattias
AU - Luben, Robert
AU - Lubke, Gitta
AU - Ludolph-Donislawski, Anja
AU - Lupoli, Sara
AU - Madden, Pamela A F
AU - Männikkö, Reija
AU - Marques-Vidal, Pedro
AU - Martin, Nicholas G.
AU - Mckenzie, Colin A
AU - McKnight, Barbara
AU - Mellström, Dan
AU - Menni, Cristina
AU - Montgomery, Grant W.
AU - Musk, Aw Bill
AU - Narisu, Narisu
AU - Nauck, Matthias
AU - Nolte, Ilja M
AU - Oldehinkel, Albertine J
AU - Olden, Matthias
AU - Ong, Ken K
AU - Padmanabhan, Sandosh
AU - Peyser, Patricia A
AU - Pisinger, Charlotta
AU - Porteous, David J
AU - Raitakari, Olli T
AU - Rankinen, Tuomo
AU - Rao, Dabeeru C
AU - Rasmussen-Torvik, Laura J
AU - Rawal, Rajesh
AU - Rice, Treva K
AU - Ridker, Paul M
AU - Rose, Lynda M
AU - Bien, Stephanie A
AU - Rudan, Igor
AU - Sanna, Serena
AU - Sarzynski, Mark A
AU - Sattar, Naveed
AU - Savonen, Kai
AU - Schlessinger, David
AU - Scholtens, Salome
AU - Schurmann, Claudia
AU - Scott, Robert A
AU - Sennblad, Bengt
AU - Siemelink, Marten A
AU - Silbernagel, Günther
AU - Slagboom, P Eline
AU - Snieder, Harold
AU - Staessen, Jan A.
AU - Stott, David J
AU - Swertz, Morris A
AU - Swift, Amy J
AU - Taylor, Kent D
AU - Tayo, Bamidele O
AU - Thorand, Barbara
AU - Thuillier, Dorothee
AU - Tuomilehto, Jaakko
AU - Uitterlinden, Andre G
AU - Vandenput, Liesbeth
AU - Vohl, Marie-Claude
AU - Völzke, Henry
AU - Vonk, Judith M
AU - Waeber, Gerard
AU - Waldenberger, Melanie
AU - Westendorp, R G J
AU - Wild, Sarah
AU - Willemsen, Gonneke
AU - Wolffenbuttel, Bruce H R
AU - Wong, Andrew
AU - Wright, Alan F
AU - Zhao, Wei
AU - Zillikens, M Carola
AU - Baldassarre, Damiano
AU - Balkau, Beverley
AU - Bandinelli, Stefania
AU - Böger, Carsten A
AU - Boomsma, Dorret I
AU - Bouchard, Claude
AU - Bruinenberg, Marcel
AU - Chasman, Daniel I
AU - Chen, Yii-DerIda
AU - Chines, Peter S
AU - Cooper, Richard S
AU - Cucca, Francesco
AU - Cusi, Daniele
AU - Faire, Ulf de
AU - Ferrucci, Luigi
AU - Franks, Paul W
AU - Froguel, Philippe
AU - Gordon-Larsen, Penny
AU - Grabe, Hans Jörgen
AU - Gudnason, Vilmundur
AU - Haiman, Christopher A
AU - Hayward, Caroline
AU - Hveem, Kristian
AU - Johnson, Andrew D
AU - Wouter Jukema, J
AU - Kardia, Sharon L R
AU - Kivimaki, Mika
AU - Kooner, Jaspal S
AU - Kuh, Diana
AU - Laakso, Markku
AU - Lehtimäki, Terho
AU - Marchand, Loic Le
AU - März, Winfried
AU - McCarthy, Mark I
AU - Metspalu, Andres
AU - Morris, Andrew P
AU - Ohlsson, Claes
AU - Palmer, Lyle J
AU - Pasterkamp, Gerard
AU - Pedersen, Oluf
AU - Peters, Annette
AU - Peters, Ulrike
AU - Polasek, Ozren
AU - Psaty, Bruce M
AU - Qi, Lu
AU - Rauramaa, Rainer
AU - Smith, Blair H
AU - Sørensen, Thorkild I A
AU - Strauch, Konstantin
AU - Tiemeier, Henning
AU - Tremoli, Elena
AU - van der Harst, Pim
AU - Vestergaard, Henrik
AU - Vollenweider, Peter
AU - Wareham, Nicholas J
AU - Weir, David R
AU - Whitfield, John B
AU - Wilson, James F
AU - Tyrrell, Jessica
AU - Frayling, Timothy M
AU - Barroso, Inês
AU - Boehnke, Michael
AU - Deloukas, Panagiotis
AU - Fox, Caroline S
AU - Hirschhorn, Joel N
AU - Hunter, David J
AU - Spector, Tim D
AU - Strachan, David P
AU - van Duijn, Cornélia M
AU - Heid, Iris M
AU - Mohlke, Karen L
AU - Marchini, Jonathan L
AU - Loos, Ruth J F
AU - Kilpeläinen, Tuomas O
AU - Liu, Ching-Ti
AU - Borecki, Ingrid B
AU - North, Kari E
AU - Cupples, L Adrienne
PY - 2017/4/26
Y1 - 2017/4/26
N2 - 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.
AB - 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.
KW - Journal Article
U2 - 10.1038/ncomms14977
DO - 10.1038/ncomms14977
M3 - Journal article
C2 - 28443625
VL - 8
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 14977
ER -