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-Møller, 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, 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 and Grant, Struan F A (2012) A genome-wide association meta-analysis identifies new childhood obesity loci. Nature Genetics, 44(5), pp. 526-531. ISSN (print) 1061-4036

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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 × 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.

Item Type: Article
Research Area: Biological sciences
Faculty, School or Research Centre: Faculty of Science, Engineering and Computing > School of Life Sciences, Pharmacy and Chemistry
Faculty of Science, Engineering and Computing
Depositing User: Jessica Buxton
Date Deposited: 28 Oct 2019 16:01
Last Modified: 28 Oct 2019 16:10
DOI: https://doi.org/10.1038/ng.2247
URI: http://eprints.kingston.ac.uk/id/eprint/40444

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