A Genome-Wide Association Meta-Analysis Identifies New Childhood Obesity Loci

Bradfield, Jonathan P.; Taal, H. Rob; Timpson, Nicholas J.; Scherag, Andre; 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; Rivadeneira, Fernando; Uitterlinden, Andre G.; van Duijn, Cornelia M.; van der Valk, Ralf J. P.; de Jongste, Johan C.; Postma, Dirkje S.; Boomsma, Dorret I.; Gauderman, W. James; Hassanein, Mohamed T.; Lindgren, Cecilia M.; Magi, Reedik; Boreham, Colin A. G.; Neville, Charlotte E.; Moreno, Luis A.; Elliott, Paul; Pouta, Anneli; Hartikainen, Anna-Liisa; Li, Mingyao; Raitakari, Olli; Lehtimaki, 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, Monica; Hirschhorn, Joel N.; Gillman, Matthew W.; Kreiner-Moller, Eskil; Bisgaard, Hans; Gilliland, Frank D.; Heinrich, Joachim; Wheeler, Eleanor; Barroso, Ines; O'Rahilly, Stephen; Meirhaeghe, Aline; Sorensen, 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., for the Early Growth Genetics (EGG) Consortium [Linda S. Adair, Member]. (2012). A Genome-Wide Association Meta-Analysis Identifies New Childhood Obesity Loci. Nature Genetics, 44(5), 526-31. PMCID: PMC3370100

Bradfield, Jonathan P.; Taal, H. Rob; Timpson, Nicholas J.; Scherag, Andre; 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; Rivadeneira, Fernando; Uitterlinden, Andre G.; van Duijn, Cornelia M.; van der Valk, Ralf J. P.; de Jongste, Johan C.; Postma, Dirkje S.; Boomsma, Dorret I.; Gauderman, W. James; Hassanein, Mohamed T.; Lindgren, Cecilia M.; Magi, Reedik; Boreham, Colin A. G.; Neville, Charlotte E.; Moreno, Luis A.; Elliott, Paul; Pouta, Anneli; Hartikainen, Anna-Liisa; Li, Mingyao; Raitakari, Olli; Lehtimaki, 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, Monica; Hirschhorn, Joel N.; Gillman, Matthew W.; Kreiner-Moller, Eskil; Bisgaard, Hans; Gilliland, Frank D.; Heinrich, Joachim; Wheeler, Eleanor; Barroso, Ines; O'Rahilly, Stephen; Meirhaeghe, Aline; Sorensen, 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., for the Early Growth Genetics (EGG) Consortium [Linda S. Adair, Member]. (2012). A Genome-Wide Association Meta-Analysis Identifies New Childhood Obesity Loci. Nature Genetics, 44(5), 526-31. PMCID: PMC3370100

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Multiple genetic variants have been associated with adult obesity and a few with severe obesity in childhood; however, less progress has been made in establishing genetic influences on common early-onset obesity. We performed a North American, Australian and European collaborative meta-analysis of 14 studies consisting of 5,530 cases (>/=95th percentile of body mass index (BMI)) and 8,318 controls (<50th percentile of BMI) of European ancestry. Taking forward the eight newly discovered signals yielding association with P < 5 x 10(-6) in nine independent data sets (2,818 cases and 4,083 controls), we observed two loci that yielded genome-wide significant combined P values near OLFM4 at 13q14 (rs9568856; P = 1.82 x 10(-9); odds ratio (OR) = 1.22) and within HOXB5 at 17q21 (rs9299; P = 3.54 x 10(-9); OR = 1.14). Both loci continued to show association when two extreme childhood obesity cohorts were included (2,214 cases and 2,674 controls). These two loci also yielded directionally consistent associations in a previous meta-analysis of adult BMI(1).


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Bradfield, Jonathan P.
Taal, H. Rob
Timpson, Nicholas J.
Scherag, Andre
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
Rivadeneira, Fernando
Uitterlinden, Andre G.
van Duijn, Cornelia M.
van der Valk, Ralf J. P.
de Jongste, Johan C.
Postma, Dirkje S.
Boomsma, Dorret I.
Gauderman, W. James
Hassanein, Mohamed T.
Lindgren, Cecilia M.
Magi, Reedik
Boreham, Colin A. G.
Neville, Charlotte E.
Moreno, Luis A.
Elliott, Paul
Pouta, Anneli
Hartikainen, Anna-Liisa
Li, Mingyao
Raitakari, Olli
Lehtimaki, 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, Monica
Hirschhorn, Joel N.
Gillman, Matthew W.
Kreiner-Moller, Eskil
Bisgaard, Hans
Gilliland, Frank D.
Heinrich, Joachim
Wheeler, Eleanor
Barroso, Ines
O'Rahilly, Stephen
Meirhaeghe, Aline
Sorensen, 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., for the Early Growth Genetics (EGG) Consortium [Linda S. Adair, Member]



2012


Nature Genetics

44

5

526-31








PMC3370100


8035

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