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. EvansBeate 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

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    297 Citations (Scopus)


    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.

    Original languageEnglish
    Pages (from-to)526-531
    Number of pages6
    JournalNature Genetics
    Issue number5
    Publication statusPublished or Issued - May 2012

    ASJC Scopus subject areas

    • Genetics

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