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A genome-wide association meta-analysis identifies new childhood obesity loci

Multiple genetic variants have been associated with adult obesity and a few with severe obesity in childhood; however, less progress has been made to establish genetic influences on common early-onset obesity. We performed a North American-Australian-European collaborative meta-analysis of fourteen...

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Autores principales: Bradfield, Jonathan P., Taal, H. Rob, Timpson, Nicholas J., Scherag, André, Lecoeur, Cecile, Warrington, Nicole M., Hypponen, Elina, Holst, Claus, Valcarcel, Beatriz, Thiering, Elisabeth, Salem, Rany M., Schumacher, Fredrick R., Cousminer, Diana L., Sleiman, Patrick M.A., Zhao, Jianhua, Berkowitz, Robert I., Vimaleswaran, Karani S., Jarick, Ivonne, Pennell, Craig E., Evans, David M., St. Pourcain, Beate, Berry, Diane J., Mook-Kanamori, Dennis O, Hofman, Albert, Rivadeinera, Fernando, Uitterlinden, André G., van Duijn, Cornelia M., van der Valk, Ralf J.P., de Jongste, Johan C., Postma, Dirkje S., Boomsma, Dorret I., Gauderman, William J., Hassanein, Mohamed T., Lindgren, Cecilia M., Mägi, Reedik, Boreham, Colin A.G., Neville, Charlotte E., Moreno, Luis A., Elliott, Paul, Pouta, Anneli, Hartikainen, Anna-Liisa, Li, Mingyao, Raitakari, Olli, Lehtimäki, Terho, Eriksson, Johan G., Palotie, Aarno, Dallongeville, Jean, Das, Shikta, Deloukas, Panos, McMahon, George, Ring, Susan M., Kemp, John P., Buxton, Jessica L., Blakemore, Alexandra I.F., Bustamante, Mariona, Guxens, Mònica, Hirschhorn, Joel N., Gillman, Matthew W., Kreiner-Møller, Eskil, Bisgaard, Hans, Gilliland, Frank D., Heinrich, Joachim, Wheeler, Eleanor, Barroso, Inês, O'Rahilly, Stephen, Meirhaeghe, Aline, Sørensen, Thorkild I.A., Power, Chris, Palmer, Lyle J., Hinney, Anke, Widen, Elisabeth, Farooqi, I. Sadaf, McCarthy, Mark I., Froguel, Philippe, Meyre, David, Hebebrand, Johannes, Jarvelin, Marjo-Riitta, Jaddoe, Vincent W.V., Smith, George Davey, Hakonarson, Hakon, Grant, Struan F.A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3370100/
https://www.ncbi.nlm.nih.gov/pubmed/22484627
http://dx.doi.org/10.1038/ng.2247
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author Bradfield, Jonathan P.
Taal, H. Rob
Timpson, Nicholas J.
Scherag, André
Lecoeur, Cecile
Warrington, Nicole M.
Hypponen, Elina
Holst, Claus
Valcarcel, Beatriz
Thiering, Elisabeth
Salem, Rany M.
Schumacher, Fredrick R.
Cousminer, Diana L.
Sleiman, Patrick M.A.
Zhao, Jianhua
Berkowitz, Robert I.
Vimaleswaran, Karani S.
Jarick, Ivonne
Pennell, Craig E.
Evans, David M.
St. Pourcain, Beate
Berry, Diane J.
Mook-Kanamori, Dennis O
Hofman, Albert
Rivadeinera, Fernando
Uitterlinden, André G.
van Duijn, Cornelia M.
van der Valk, Ralf J.P.
de Jongste, Johan C.
Postma, Dirkje S.
Boomsma, Dorret I.
Gauderman, William J.
Hassanein, Mohamed T.
Lindgren, Cecilia M.
Mägi, Reedik
Boreham, Colin A.G.
Neville, Charlotte E.
Moreno, Luis A.
Elliott, Paul
Pouta, Anneli
Hartikainen, Anna-Liisa
Li, Mingyao
Raitakari, Olli
Lehtimäki, Terho
Eriksson, Johan G.
Palotie, Aarno
Dallongeville, Jean
Das, Shikta
Deloukas, Panos
McMahon, George
Ring, Susan M.
Kemp, John P.
Buxton, Jessica L.
Blakemore, Alexandra I.F.
Bustamante, Mariona
Guxens, Mònica
Hirschhorn, Joel N.
Gillman, Matthew W.
Kreiner-Møller, Eskil
Bisgaard, Hans
Gilliland, Frank D.
Heinrich, Joachim
Wheeler, Eleanor
Barroso, Inês
O'Rahilly, Stephen
Meirhaeghe, Aline
Sørensen, Thorkild I.A.
Power, Chris
Palmer, Lyle J.
Hinney, Anke
Widen, Elisabeth
Farooqi, I. Sadaf
McCarthy, Mark I.
Froguel, Philippe
Meyre, David
Hebebrand, Johannes
Jarvelin, Marjo-Riitta
Jaddoe, Vincent W.V.
Smith, George Davey
Hakonarson, Hakon
Grant, Struan F.A.
author_facet Bradfield, Jonathan P.
Taal, H. Rob
Timpson, Nicholas J.
Scherag, André
Lecoeur, Cecile
Warrington, Nicole M.
Hypponen, Elina
Holst, Claus
Valcarcel, Beatriz
Thiering, Elisabeth
Salem, Rany M.
Schumacher, Fredrick R.
Cousminer, Diana L.
Sleiman, Patrick M.A.
Zhao, Jianhua
Berkowitz, Robert I.
Vimaleswaran, Karani S.
Jarick, Ivonne
Pennell, Craig E.
Evans, David M.
St. Pourcain, Beate
Berry, Diane J.
Mook-Kanamori, Dennis O
Hofman, Albert
Rivadeinera, Fernando
Uitterlinden, André G.
van Duijn, Cornelia M.
van der Valk, Ralf J.P.
de Jongste, Johan C.
Postma, Dirkje S.
Boomsma, Dorret I.
Gauderman, William J.
Hassanein, Mohamed T.
Lindgren, Cecilia M.
Mägi, Reedik
Boreham, Colin A.G.
Neville, Charlotte E.
Moreno, Luis A.
Elliott, Paul
Pouta, Anneli
Hartikainen, Anna-Liisa
Li, Mingyao
Raitakari, Olli
Lehtimäki, Terho
Eriksson, Johan G.
Palotie, Aarno
Dallongeville, Jean
Das, Shikta
Deloukas, Panos
McMahon, George
Ring, Susan M.
Kemp, John P.
Buxton, Jessica L.
Blakemore, Alexandra I.F.
Bustamante, Mariona
Guxens, Mònica
Hirschhorn, Joel N.
Gillman, Matthew W.
Kreiner-Møller, Eskil
Bisgaard, Hans
Gilliland, Frank D.
Heinrich, Joachim
Wheeler, Eleanor
Barroso, Inês
O'Rahilly, Stephen
Meirhaeghe, Aline
Sørensen, Thorkild I.A.
Power, Chris
Palmer, Lyle J.
Hinney, Anke
Widen, Elisabeth
Farooqi, I. Sadaf
McCarthy, Mark I.
Froguel, Philippe
Meyre, David
Hebebrand, Johannes
Jarvelin, Marjo-Riitta
Jaddoe, Vincent W.V.
Smith, George Davey
Hakonarson, Hakon
Grant, Struan F.A.
author_sort Bradfield, Jonathan P.
collection PubMed
description Multiple genetic variants have been associated with adult obesity and a few with severe obesity in childhood; however, less progress has been made to establish genetic influences on common early-onset obesity. We performed a North American-Australian-European collaborative meta-analysis of fourteen studies consisting of 5,530 cases (≥95(th) percentile of body mass index (BMI)) and 8,318 controls (<50(th) percentile of BMI) of European ancestry. Taking forward the eight novel signals yielding association with P < 5×10(−6) in to nine independent datasets (n = 2,818 cases and 4,083 controls) we observed two loci that yielded a genome wide significant combined P-value, namely near OLFM4 on 13q14 (rs9568856; P=1.82×10(−9); OR=1.22) and within HOXB5 on 17q21 (rs9299; P=3.54×10(−9); OR=1.14). Both loci continued to show association when including two extreme childhood obesity cohorts (n = 2,214 cases and 2,674 controls). Finally, these two loci yielded directionally consistent associations in the GIANT meta-analysis of adult BMI(1).
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spelling pubmed-33701002012-07-01 A genome-wide association meta-analysis identifies new childhood obesity loci Bradfield, Jonathan P. Taal, H. Rob Timpson, Nicholas J. Scherag, André Lecoeur, Cecile Warrington, Nicole M. Hypponen, Elina Holst, Claus Valcarcel, Beatriz Thiering, Elisabeth Salem, Rany M. Schumacher, Fredrick R. Cousminer, Diana L. Sleiman, Patrick M.A. Zhao, Jianhua Berkowitz, Robert I. Vimaleswaran, Karani S. Jarick, Ivonne Pennell, Craig E. Evans, David M. St. Pourcain, Beate Berry, Diane J. Mook-Kanamori, Dennis O Hofman, Albert Rivadeinera, Fernando Uitterlinden, André G. van Duijn, Cornelia M. van der Valk, Ralf J.P. de Jongste, Johan C. Postma, Dirkje S. Boomsma, Dorret I. Gauderman, William J. Hassanein, Mohamed T. Lindgren, Cecilia M. Mägi, Reedik Boreham, Colin A.G. Neville, Charlotte E. Moreno, Luis A. Elliott, Paul Pouta, Anneli Hartikainen, Anna-Liisa Li, Mingyao Raitakari, Olli Lehtimäki, Terho Eriksson, Johan G. Palotie, Aarno Dallongeville, Jean Das, Shikta Deloukas, Panos McMahon, George Ring, Susan M. Kemp, John P. Buxton, Jessica L. Blakemore, Alexandra I.F. Bustamante, Mariona Guxens, Mònica Hirschhorn, Joel N. Gillman, Matthew W. Kreiner-Møller, Eskil Bisgaard, Hans Gilliland, Frank D. Heinrich, Joachim Wheeler, Eleanor Barroso, Inês O'Rahilly, Stephen Meirhaeghe, Aline Sørensen, Thorkild I.A. Power, Chris Palmer, Lyle J. Hinney, Anke Widen, Elisabeth Farooqi, I. Sadaf McCarthy, Mark I. Froguel, Philippe Meyre, David Hebebrand, Johannes Jarvelin, Marjo-Riitta Jaddoe, Vincent W.V. Smith, George Davey Hakonarson, Hakon Grant, Struan F.A. Nat Genet Article Multiple genetic variants have been associated with adult obesity and a few with severe obesity in childhood; however, less progress has been made to establish genetic influences on common early-onset obesity. We performed a North American-Australian-European collaborative meta-analysis of fourteen studies consisting of 5,530 cases (≥95(th) percentile of body mass index (BMI)) and 8,318 controls (<50(th) percentile of BMI) of European ancestry. Taking forward the eight novel signals yielding association with P < 5×10(−6) in to nine independent datasets (n = 2,818 cases and 4,083 controls) we observed two loci that yielded a genome wide significant combined P-value, namely near OLFM4 on 13q14 (rs9568856; P=1.82×10(−9); OR=1.22) and within HOXB5 on 17q21 (rs9299; P=3.54×10(−9); OR=1.14). Both loci continued to show association when including two extreme childhood obesity cohorts (n = 2,214 cases and 2,674 controls). Finally, these two loci yielded directionally consistent associations in the GIANT meta-analysis of adult BMI(1). 2012-05 /pmc/articles/PMC3370100/ /pubmed/22484627 http://dx.doi.org/10.1038/ng.2247 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Bradfield, Jonathan P.
Taal, H. Rob
Timpson, Nicholas J.
Scherag, André
Lecoeur, Cecile
Warrington, Nicole M.
Hypponen, Elina
Holst, Claus
Valcarcel, Beatriz
Thiering, Elisabeth
Salem, Rany M.
Schumacher, Fredrick R.
Cousminer, Diana L.
Sleiman, Patrick M.A.
Zhao, Jianhua
Berkowitz, Robert I.
Vimaleswaran, Karani S.
Jarick, Ivonne
Pennell, Craig E.
Evans, David M.
St. Pourcain, Beate
Berry, Diane J.
Mook-Kanamori, Dennis O
Hofman, Albert
Rivadeinera, Fernando
Uitterlinden, André G.
van Duijn, Cornelia M.
van der Valk, Ralf J.P.
de Jongste, Johan C.
Postma, Dirkje S.
Boomsma, Dorret I.
Gauderman, William J.
Hassanein, Mohamed T.
Lindgren, Cecilia M.
Mägi, Reedik
Boreham, Colin A.G.
Neville, Charlotte E.
Moreno, Luis A.
Elliott, Paul
Pouta, Anneli
Hartikainen, Anna-Liisa
Li, Mingyao
Raitakari, Olli
Lehtimäki, Terho
Eriksson, Johan G.
Palotie, Aarno
Dallongeville, Jean
Das, Shikta
Deloukas, Panos
McMahon, George
Ring, Susan M.
Kemp, John P.
Buxton, Jessica L.
Blakemore, Alexandra I.F.
Bustamante, Mariona
Guxens, Mònica
Hirschhorn, Joel N.
Gillman, Matthew W.
Kreiner-Møller, Eskil
Bisgaard, Hans
Gilliland, Frank D.
Heinrich, Joachim
Wheeler, Eleanor
Barroso, Inês
O'Rahilly, Stephen
Meirhaeghe, Aline
Sørensen, Thorkild I.A.
Power, Chris
Palmer, Lyle J.
Hinney, Anke
Widen, Elisabeth
Farooqi, I. Sadaf
McCarthy, Mark I.
Froguel, Philippe
Meyre, David
Hebebrand, Johannes
Jarvelin, Marjo-Riitta
Jaddoe, Vincent W.V.
Smith, George Davey
Hakonarson, Hakon
Grant, Struan F.A.
A genome-wide association meta-analysis identifies new childhood obesity loci
title A genome-wide association meta-analysis identifies new childhood obesity loci
title_full A genome-wide association meta-analysis identifies new childhood obesity loci
title_fullStr A genome-wide association meta-analysis identifies new childhood obesity loci
title_full_unstemmed A genome-wide association meta-analysis identifies new childhood obesity loci
title_short A genome-wide association meta-analysis identifies new childhood obesity loci
title_sort genome-wide association meta-analysis identifies new childhood obesity loci
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3370100/
https://www.ncbi.nlm.nih.gov/pubmed/22484627
http://dx.doi.org/10.1038/ng.2247
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AT widenelisabeth genomewideassociationmetaanalysisidentifiesnewchildhoodobesityloci
AT farooqiisadaf genomewideassociationmetaanalysisidentifiesnewchildhoodobesityloci
AT mccarthymarki genomewideassociationmetaanalysisidentifiesnewchildhoodobesityloci
AT froguelphilippe genomewideassociationmetaanalysisidentifiesnewchildhoodobesityloci
AT meyredavid genomewideassociationmetaanalysisidentifiesnewchildhoodobesityloci
AT hebebrandjohannes genomewideassociationmetaanalysisidentifiesnewchildhoodobesityloci
AT jarvelinmarjoriitta genomewideassociationmetaanalysisidentifiesnewchildhoodobesityloci
AT jaddoevincentwv genomewideassociationmetaanalysisidentifiesnewchildhoodobesityloci
AT smithgeorgedavey genomewideassociationmetaanalysisidentifiesnewchildhoodobesityloci
AT hakonarsonhakon genomewideassociationmetaanalysisidentifiesnewchildhoodobesityloci
AT grantstruanfa genomewideassociationmetaanalysisidentifiesnewchildhoodobesityloci
AT genomewideassociationmetaanalysisidentifiesnewchildhoodobesityloci