A genome-wide association meta-analysis identifies new childhood obesity loci Academic Article uri icon

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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(1).

authors

  • 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 MA
  • 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 JP
  • de Jongste, Johan C
  • Postma, Dirkje S
  • Boomsma, Dorret I
  • Gauderman, W James
  • Hassanein, Mohamed T
  • Lindgren, Cecilia M
  • Mägi, Reedik
  • Boreham, Colin AG
  • 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 IF
  • 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 IA
  • Power, Chris
  • Palmer, Lyle J
  • Hinney, Anke
  • Widen, Elisabeth
  • Farooqi, I Sadaf
  • McCarthy, Mark I
  • Froguel, Philippe
  • Meyre, David Jean-Claude
  • Hebebrand, Johannes
  • Jarvelin, Marjo-Riitta
  • Jaddoe, Vincent WV
  • Smith, George Davey
  • Hakonarson, Hakon
  • Grant, Struan FA
  • Early Growth Genetics Consortium

publication date

  • May 2012