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

Multiple genetic variants have been associated with adult obesity and a few with severe obesity in childhood; however, less progress has been made to establish genetic influences on common early-onset obesity. We performed a North American-Australian-European collaborative meta-analysis of fourteen...

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Detalles Bibliográficos
Autores principales: 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, Rivadeinera, 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, William J., 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, Grant, Struan F.A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2012
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3370100/
https://www.ncbi.nlm.nih.gov/pubmed/22484627
http://dx.doi.org/10.1038/ng.2247
Descripción
Sumario:Multiple genetic variants have been associated with adult obesity and a few with severe obesity in childhood; however, less progress has been made to establish genetic influences on common early-onset obesity. We performed a North American-Australian-European collaborative meta-analysis of fourteen studies consisting of 5,530 cases (≥95(th) percentile of body mass index (BMI)) and 8,318 controls (<50(th) percentile of BMI) of European ancestry. Taking forward the eight novel signals yielding association with P < 5×10(−6) in to nine independent datasets (n = 2,818 cases and 4,083 controls) we observed two loci that yielded a genome wide significant combined P-value, namely near OLFM4 on 13q14 (rs9568856; P=1.82×10(−9); OR=1.22) and within HOXB5 on 17q21 (rs9299; P=3.54×10(−9); OR=1.14). Both loci continued to show association when including two extreme childhood obesity cohorts (n = 2,214 cases and 2,674 controls). Finally, these two loci yielded directionally consistent associations in the GIANT meta-analysis of adult BMI(1).

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