Authors:
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, 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-Møller, 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, Elisabeth Widen, I Sadaf Farooqi, Mark I McCarthy, Philippe Froguel, David Meyre, Johannes Hebebrand, Marjo-Riitta Jarvelin, Vincent W V Jaddoe, George Davey Smith, Hakon Hakonarson, & Struan F A Grant for the Early Growth Genetics (EGG) Consortium
Summary:
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.
Source:
Nature Genetics; 44, 526-531 (04/08/12)