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

Jonathan P. Bradfield, H. Rob Taal, Nicholas J. Timpson, André Scherag, Cecile Lecoeur, Nicole M. Warrington, Elina Hypponen, Claus Holst, Beatriz Valcarcel, Elisabeth Thiering, Rany M. Salem, Fredrick R. Schumacher, Diana L. Cousminer, Patrick M A Sleiman, Jianhua Zhao, Robert I. Berkowitz, Karani S. Vimaleswaran, Ivonne Jarick, Craig E. Pennell, David M. Evans & 59 others Beate St Pourcain, Diane J. Berry, Dennis O. Mook-Kanamori, Albert Hofman, Fernando Rivadeneira, André G. Uitterlinden, Cornelia M. Van Duijn, Ralf J P Van Der Valk, Johan C. De Jongste, Dirkje S. Postma, Dorret I. Boomsma, W. James Gauderman, Mohamed T. Hassanein, Cecilia M. Lindgren, Reedik Mägi, Colin A G Boreham, Charlotte E. Neville, Luis A. Moreno, Paul Elliott, Anneli Pouta, Anna Liisa Hartikainen, Mingyao Li, Olli Raitakari, Terho Lehtimäki, Johan G. Eriksson, Aarno Palotie, Jean Dallongeville, Shikta Das, Panos Deloukas, George Mcmahon, Susan M. Ring, John P. Kemp, Jessica L. Buxton, Alexandra I F Blakemore, Mariona Bustamante, Mònica Guxens, Joel N. Hirschhorn, Matthew W. Gillman, Eskil Kreiner-Müller, Hans Bisgaard, Frank D. Gilliland, Joachim Heinrich, Eleanor Wheeler, Inês Barroso, Stephen O'rahilly, Aline Meirhaeghe, Thorkild I A Sørensen, Chris Power, Lyle J. Palmer, Anke Hinney, I. Sadaf Farooqi, Mark I. Mccarthy, Philippe Froguel, David Meyre, Johannes Hebebrand, Marjo Riitta Jarvelin, George Davey Smith, Hakon Hakonarson, Struan F A Grant

    Research output: Contribution to journalArticle

    212 Citations (Scopus)

    Abstract

    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 × 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 × 10 -9; odds ratio (OR) = 1.22) and within HOXB5 at 17q21 (rs9299; P = 3.54 × 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.

    LanguageEnglish
    Pages526-531
    Number of pages6
    JournalNature Genetics
    Volume44
    Issue number5
    DOIs
    Publication statusPublished - 1 May 2012

    ASJC Scopus subject areas

    • Genetics

    Cite this

    Bradfield, J. P., Taal, H. R., Timpson, N. J., Scherag, A., Lecoeur, C., Warrington, N. M., ... Grant, S. F. A. (2012). A genome-wide association meta-analysis identifies new childhood obesity loci. Nature Genetics, 44(5), 526-531. https://doi.org/10.1038/ng.2247
    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 ; Rivadeneira, 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, W. James ; 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-Müller, 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 ; Farooqi, I. Sadaf ; Mccarthy, Mark I. ; Froguel, Philippe ; Meyre, David ; Hebebrand, Johannes ; Jarvelin, Marjo Riitta ; Smith, George Davey ; Hakonarson, Hakon ; Grant, Struan F A. / A genome-wide association meta-analysis identifies new childhood obesity loci. In: Nature Genetics. 2012 ; Vol. 44, No. 5. pp. 526-531.
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    Bradfield, JP, Taal, HR, Timpson, NJ, Scherag, A, Lecoeur, C, Warrington, NM, Hypponen, E, Holst, C, Valcarcel, B, Thiering, E, Salem, RM, Schumacher, FR, Cousminer, DL, Sleiman, PMA, Zhao, J, Berkowitz, RI, Vimaleswaran, KS, Jarick, I, Pennell, CE, Evans, DM, St Pourcain, B, Berry, DJ, Mook-Kanamori, DO, Hofman, A, Rivadeneira, F, Uitterlinden, AG, Van Duijn, CM, Van Der Valk, RJP, De Jongste, JC, Postma, DS, Boomsma, DI, Gauderman, WJ, Hassanein, MT, Lindgren, CM, Mägi, R, Boreham, CAG, Neville, CE, Moreno, LA, Elliott, P, Pouta, A, Hartikainen, AL, Li, M, Raitakari, O, Lehtimäki, T, Eriksson, JG, Palotie, A, Dallongeville, J, Das, S, Deloukas, P, Mcmahon, G, Ring, SM, Kemp, JP, Buxton, JL, Blakemore, AIF, Bustamante, M, Guxens, M, Hirschhorn, JN, Gillman, MW, Kreiner-Müller, E, Bisgaard, H, Gilliland, FD, Heinrich, J, Wheeler, E, Barroso, I, O'rahilly, S, Meirhaeghe, A, Sørensen, TIA, Power, C, Palmer, LJ, Hinney, A, Farooqi, IS, Mccarthy, MI, Froguel, P, Meyre, D, Hebebrand, J, Jarvelin, MR, Smith, GD, Hakonarson, H & Grant, SFA 2012, 'A genome-wide association meta-analysis identifies new childhood obesity loci', Nature Genetics, vol. 44, no. 5, pp. 526-531. https://doi.org/10.1038/ng.2247

    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; Rivadeneira, 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, W. James; 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-Müller, 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; Farooqi, I. Sadaf; Mccarthy, Mark I.; Froguel, Philippe; Meyre, David; Hebebrand, Johannes; Jarvelin, Marjo Riitta; Smith, George Davey; Hakonarson, Hakon; Grant, Struan F A.

    In: Nature Genetics, Vol. 44, No. 5, 01.05.2012, p. 526-531.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - A genome-wide association meta-analysis identifies new childhood obesity loci

    AU - Bradfield, Jonathan P.

    AU - Taal, H. Rob

    AU - Timpson, Nicholas J.

    AU - Scherag, André

    AU - Lecoeur, Cecile

    AU - Warrington, Nicole M.

    AU - Hypponen, Elina

    AU - Holst, Claus

    AU - Valcarcel, Beatriz

    AU - Thiering, Elisabeth

    AU - Salem, Rany M.

    AU - Schumacher, Fredrick R.

    AU - Cousminer, Diana L.

    AU - Sleiman, Patrick M A

    AU - Zhao, Jianhua

    AU - Berkowitz, Robert I.

    AU - Vimaleswaran, Karani S.

    AU - Jarick, Ivonne

    AU - Pennell, Craig E.

    AU - Evans, David M.

    AU - St Pourcain, Beate

    AU - Berry, Diane J.

    AU - Mook-Kanamori, Dennis O.

    AU - Hofman, Albert

    AU - Rivadeneira, Fernando

    AU - Uitterlinden, André G.

    AU - Van Duijn, Cornelia M.

    AU - Van Der Valk, Ralf J P

    AU - De Jongste, Johan C.

    AU - Postma, Dirkje S.

    AU - Boomsma, Dorret I.

    AU - Gauderman, W. James

    AU - Hassanein, Mohamed T.

    AU - Lindgren, Cecilia M.

    AU - Mägi, Reedik

    AU - Boreham, Colin A G

    AU - Neville, Charlotte E.

    AU - Moreno, Luis A.

    AU - Elliott, Paul

    AU - Pouta, Anneli

    AU - Hartikainen, Anna Liisa

    AU - Li, Mingyao

    AU - Raitakari, Olli

    AU - Lehtimäki, Terho

    AU - Eriksson, Johan G.

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    AU - Dallongeville, Jean

    AU - Das, Shikta

    AU - Deloukas, Panos

    AU - Mcmahon, George

    AU - Ring, Susan M.

    AU - Kemp, John P.

    AU - Buxton, Jessica L.

    AU - Blakemore, Alexandra I F

    AU - Bustamante, Mariona

    AU - Guxens, Mònica

    AU - Hirschhorn, Joel N.

    AU - Gillman, Matthew W.

    AU - Kreiner-Müller, Eskil

    AU - Bisgaard, Hans

    AU - Gilliland, Frank D.

    AU - Heinrich, Joachim

    AU - Wheeler, Eleanor

    AU - Barroso, Inês

    AU - O'rahilly, Stephen

    AU - Meirhaeghe, Aline

    AU - Sørensen, Thorkild I A

    AU - Power, Chris

    AU - Palmer, Lyle J.

    AU - Hinney, Anke

    AU - Farooqi, I. Sadaf

    AU - Mccarthy, Mark I.

    AU - Froguel, Philippe

    AU - Meyre, David

    AU - Hebebrand, Johannes

    AU - Jarvelin, Marjo Riitta

    AU - Smith, George Davey

    AU - Hakonarson, Hakon

    AU - Grant, Struan F A

    PY - 2012/5/1

    Y1 - 2012/5/1

    N2 - 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 × 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 × 10 -9; odds ratio (OR) = 1.22) and within HOXB5 at 17q21 (rs9299; P = 3.54 × 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.

    AB - 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 × 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 × 10 -9; odds ratio (OR) = 1.22) and within HOXB5 at 17q21 (rs9299; P = 3.54 × 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.

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    Bradfield JP, Taal HR, Timpson NJ, Scherag A, Lecoeur C, Warrington NM et al. A genome-wide association meta-analysis identifies new childhood obesity loci. Nature Genetics. 2012 May 1;44(5):526-531. https://doi.org/10.1038/ng.2247