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 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, Early Growth Genetics Consortium, Linda S Adair, Wei Ang, Mustafa Atalay, Toos van Beijsterveldt, Nienke Bergen, Kelly Benke, Diane Berry, Jonathan Bradfield, Mariona Bustamente, Pimphen Charoen, Lachlan Coin, Diana Cousminer, Shikta Das, Oliver S P Davis, Paul Elliott, Dave M Evans, Bjarke Feenstra, Claudia Flexeder, Tim Frayling, Rachel Freathy, Romy Gaillard, Frank Geller, Maria Groen-Blokhuis, Liang-Kee Goh, Mònica Guxens, Claire M A Haworth, Dexter Hadley, Johannes Hedebrand, Anke Hinney, Joel N Hirschhorn, John W Holloway, Claus Holst, Jouke Jan Hottenga, Momoko Horikoshi, Ville Huikari, Elina Hypponen, Carmen Iñiguez, Marika Kaakinen, Tuomas O Kilpeläinen, Mirna Kirin, Mattew Kowgier, Hanna-Maaria Lakka, Leslie A Lange, Debbie A Lawlor, Terho Lehtimäki, Alex Lewin, Cecilia Lindgren, Virpi Lindi, Reedik Mägi, Julie Marsh, Christel Middeldorp, Iona Millwood, Dennis O Mook-Kanamori, Jeffrey C Murray, Michel Nivard, Ellen Aagaard Nohr, Ioanna Ntalla, Emily Oken, Paul O'Reilly, Lyle Palmer, Kalliope Panoutsopoulou, Jennifer Pararajasingham, Inga Prokopenko, Alina Rodriguez, Rany M Salem, Sylvain Sebert, Niina Siitonen, Ulla Sovio, Beate St Pourcain, David P Strachan, Jordi Sunyer, H Rob Taal, Yik-Ying Teo, Elisabeth Thiering, Carla Tiesler, Andre G Uitterlinden, Beatriz Valcárcel, Nicole Warrington, Scott White, Gonneke Willemsen, Hanieh Yaghootkar, Eleftheria Zeggini, Dorret I Boomsma, Cyrus Cooper, Xavier Estivill, Matthew Gillman, Struan F A Grant, Hakon Hakonarson, Andrew T Hattersley, Joachim Heinrich, Berthold Hocher, Vincent W V Jaddoe, Marjo-Riitta Jarvelin, Timo A Lakka, Mark I McCarthy, Mads Melbye, Karen L Mohlke, George V Dedoussis, Ken K Ong, Ewan R Pearson, Craig E Pennell, Thomas S Price, Chris Power, Olli T Raitakari, Seang-Mei Saw, Andre Scherag, Olli Simell, Thorkild I A Sørensen, Jordi Sunyer, Nicholas J Timpson, Elisabeth Widen, James F Wilson, 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, Early Growth Genetics Consortium, Linda S Adair, Wei Ang, Mustafa Atalay, Toos van Beijsterveldt, Nienke Bergen, Kelly Benke, Diane Berry, Jonathan Bradfield, Mariona Bustamente, Pimphen Charoen, Lachlan Coin, Diana Cousminer, Shikta Das, Oliver S P Davis, Paul Elliott, Dave M Evans, Bjarke Feenstra, Claudia Flexeder, Tim Frayling, Rachel Freathy, Romy Gaillard, Frank Geller, Maria Groen-Blokhuis, Liang-Kee Goh, Mònica Guxens, Claire M A Haworth, Dexter Hadley, Johannes Hedebrand, Anke Hinney, Joel N Hirschhorn, John W Holloway, Claus Holst, Jouke Jan Hottenga, Momoko Horikoshi, Ville Huikari, Elina Hypponen, Carmen Iñiguez, Marika Kaakinen, Tuomas O Kilpeläinen, Mirna Kirin, Mattew Kowgier, Hanna-Maaria Lakka, Leslie A Lange, Debbie A Lawlor, Terho Lehtimäki, Alex Lewin, Cecilia Lindgren, Virpi Lindi, Reedik Mägi, Julie Marsh, Christel Middeldorp, Iona Millwood, Dennis O Mook-Kanamori, Jeffrey C Murray, Michel Nivard, Ellen Aagaard Nohr, Ioanna Ntalla, Emily Oken, Paul O'Reilly, Lyle Palmer, Kalliope Panoutsopoulou, Jennifer Pararajasingham, Inga Prokopenko, Alina Rodriguez, Rany M Salem, Sylvain Sebert, Niina Siitonen, Ulla Sovio, Beate St Pourcain, David P Strachan, Jordi Sunyer, H Rob Taal, Yik-Ying Teo, Elisabeth Thiering, Carla Tiesler, Andre G Uitterlinden, Beatriz Valcárcel, Nicole Warrington, Scott White, Gonneke Willemsen, Hanieh Yaghootkar, Eleftheria Zeggini, Dorret I Boomsma, Cyrus Cooper, Xavier Estivill, Matthew Gillman, Struan F A Grant, Hakon Hakonarson, Andrew T Hattersley, Joachim Heinrich, Berthold Hocher, Vincent W V Jaddoe, Marjo-Riitta Jarvelin, Timo A Lakka, Mark I McCarthy, Mads Melbye, Karen L Mohlke, George V Dedoussis, Ken K Ong, Ewan R Pearson, Craig E Pennell, Thomas S Price, Chris Power, Olli T Raitakari, Seang-Mei Saw, Andre Scherag, Olli Simell, Thorkild I A Sørensen, Jordi Sunyer, Nicholas J Timpson, Elisabeth Widen, James F Wilson

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).

Figures

Figure 1
Figure 1
Manhattan Plot of the meta-analysis of childhood obesity GWAS runs in the discovery stage (5,530 cases and 8,318 controls), with each locus achieving genome wide significance (P < 5×10−8) indicated in black text. In addition, the novel loci uncovered in this study are indicated in red text.

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Source: PubMed

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