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

Alexandra I F Blakemore; Mariona Bustamante; M├▓nica 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; Colin A G Boreham; Charlotte E Neville; Luis A Moreno; Paul Elliott; Anneli Pouta; Anna-Liisa Hartikainen; Mingyao Li; Olli Raitakari; Terho Lehtim├ñki; Johan G Eriksson; Aarno Palotie; Jean Dallongeville; Shikta Das; Panos Deloukas; George McMahon; Susan M Ring; John P Kemp; Jessica L Buxton; H Rob Taal; Nicholas J Timpson; Jonathan P Bradfield; Andr├® 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; Andr├® 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 M├ñgi

doi:10.1038/ng.2247

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

Alexandra I F Blakemore
, Mariona Bustamante
, M├▓nica 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, Colin A G Boreham, Charlotte E Neville, Luis A Moreno, Paul Elliott, Anneli Pouta, Anna-Liisa Hartikainen, Mingyao Li, Olli Raitakari, Terho Lehtim├ñki, Johan G Eriksson, Aarno Palotie, Jean Dallongeville, Shikta Das, Panos Deloukas, George McMahon, Susan M Ring, John P Kemp, Jessica L Buxton, H Rob Taal, Nicholas J Timpson, Jonathan P Bradfield, Andr├® 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, Andr├® 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 M├ñgi

Research output: Contribution to journal › Article › peer-review

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 (ÔëÑ95th 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.

Original language	English
Pages (from-to)	526-531
Journal	Nature Genetics
Volume	44
Issue number	5
Early online date	8 Apr 2012
DOIs	https://doi.org/10.1038/ng.2247
Publication status	Published - 31 May 2012

Keywords

Biological sciences

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10.1038/ng.2247

https://doi.org/10.1038/ng.2247

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Blakemore, A. I. F., Bustamante, M., Guxens, M., Hirschhorn, J. N., Gillman, M. W., Kreiner-Møller, E., Bisgaard, H., Gilliland, F. D., Heinrich, J., Wheeler, E., Barroso, I., O'Rahilly, S., Meirhaeghe, A., Sørensen, T. I. A., Power, C., Palmer, L. J., Hinney, A., Widen, E., Farooqi, I. S., ... M├ñgi, R. (2012). A genome-wide association meta-analysis identifies new childhood obesity loci. Nature Genetics, 44(5), 526-531. https://doi.org/10.1038/ng.2247

@article{95a47259dcf9462492844380d8135010,

title = "A genome-wide association meta-analysis identifies new childhood obesity loci",

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 ({\^O}{\"e}{\~N}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.",

keywords = "Biological sciences",

author = "Blakemore, \{Alexandra I F\} and Mariona Bustamante and M├▓nica Guxens and Hirschhorn, \{Joel N\} and Gillman, \{Matthew W\} and Eskil Kreiner-M{\o}ller and Hans Bisgaard and Gilliland, \{Frank D\} and Joachim Heinrich and Eleanor Wheeler and In{\^e}s Barroso and Stephen O'Rahilly and Aline Meirhaeghe and S{\o}rensen, \{Thorkild I A\} and Chris Power and Palmer, \{Lyle J\} and Anke Hinney and Elisabeth Widen and Farooqi, \{I Sadaf\} and McCarthy, \{Mark I\} and Philippe Froguel and David Meyre and Johannes Hebebrand and Marjo-Riitta Jarvelin and Jaddoe, \{Vincent W V\} and Smith, \{George Davey\} and Hakon Hakonarson and Grant, \{Struan F A\} and Boreham, \{Colin A G\} and Neville, \{Charlotte E\} and Moreno, \{Luis A\} and Paul Elliott and Anneli Pouta and Anna-Liisa Hartikainen and Mingyao Li and Olli Raitakari and Terho Lehtim├{\~n}ki and Eriksson, \{Johan G\} and Aarno Palotie and Jean Dallongeville and Shikta Das and Panos Deloukas and George McMahon and Ring, \{Susan M\} and Kemp, \{John P\} and Buxton, \{Jessica L\} and Taal, \{H Rob\} and Timpson, \{Nicholas J\} and Bradfield, \{Jonathan P\} and Andr├{\textregistered} Scherag and Cecile Lecoeur and Warrington, \{Nicole M\} and Elina Hypponen and Claus Holst and Beatriz Valcarcel and Elisabeth Thiering and Salem, \{Rany M\} and Schumacher, \{Fredrick R\} and Cousminer, \{Diana L\} and Sleiman, \{Patrick M A\} and Jianhua Zhao and Berkowitz, \{Robert I\} and Vimaleswaran, \{Karani S\} and Ivonne Jarick and Pennell, \{Craig E\} and Evans, \{David M\} and \{St Pourcain\}, Beate and Berry, \{Diane J\} and Mook-Kanamori, \{Dennis O\} and Albert Hofman and Fernando Rivadeneira and Uitterlinden, \{Andr├{\textregistered} G\} and \{van Duijn\}, \{Cornelia M\} and \{van der Valk\}, \{Ralf J P\} and \{de Jongste\}, \{Johan C\} and Postma, \{Dirkje S\} and Boomsma, \{Dorret I\} and Gauderman, \{W James\} and Hassanein, \{Mohamed T\} and Lindgren, \{Cecilia M\} and Reedik M├{\~n}gi",

year = "2012",

month = may,

day = "31",

doi = "10.1038/ng.2247",

language = "English",

volume = "44",

pages = "526--531",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "5",

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Blakemore, AIF, Bustamante, M, Guxens, M, Hirschhorn, JN, Gillman, MW, Kreiner-Møller, E, Bisgaard, H, Gilliland, FD, Heinrich, J, Wheeler, E, Barroso, I, O'Rahilly, S, Meirhaeghe, A, Sørensen, TIA, Power, C, Palmer, LJ, Hinney, A, Widen, E, Farooqi, IS, McCarthy, MI, Froguel, P, Meyre, D, Hebebrand, J, Jarvelin, M-R, Jaddoe, VWV, Smith, GD, Hakonarson, H, Grant, SFA, Boreham, CAG, Neville, CE, Moreno, LA, Elliott, P, Pouta, A, Hartikainen, A-L, Li, M, Raitakari, O, Lehtim├ñki, T, Eriksson, JG, Palotie, A, Dallongeville, J, Das, S, Deloukas, P, McMahon, G, Ring, SM, Kemp, JP, Buxton, JL, Taal, HR, Timpson, NJ, Bradfield, JP, Scherag, A, Lecoeur, C, Warrington, NM, Hypponen, E, Holst, C, Valcarcel, B, Thiering, E, Salem, RM, Schumacher, FR, Cousminer, DL, Sleiman, PMA, Zhao, J, Berkowitz, RI, Vimaleswaran, KS, Jarick, I, Pennell, CE, Evans, DM, St Pourcain, B, Berry, DJ, Mook-Kanamori, DO, Hofman, A, Rivadeneira, F, Uitterlinden, AG, van Duijn, CM, van der Valk, RJP, de Jongste, JC, Postma, DS, Boomsma, DI, Gauderman, WJ, Hassanein, MT, Lindgren, CM & M├ñgi, R 2012, 'A genome-wide association meta-analysis identifies new childhood obesity loci', Nature Genetics, vol. 44, no. 5, pp. 526-531. https://doi.org/10.1038/ng.2247

TY - JOUR

T1 - A genome-wide association meta-analysis identifies new childhood obesity loci

AU - Blakemore, Alexandra I F

AU - Bustamante, Mariona

AU - Guxens, M├▓nica

AU - Hirschhorn, Joel N

AU - Gillman, Matthew W

AU - Kreiner-Møller, Eskil

AU - Bisgaard, Hans

AU - Gilliland, Frank D

AU - Heinrich, Joachim

AU - Wheeler, Eleanor

AU - Barroso, Inês

AU - O'Rahilly, Stephen

AU - Meirhaeghe, Aline

AU - Sørensen, Thorkild I A

AU - Power, Chris

AU - Palmer, Lyle J

AU - Hinney, Anke

AU - Widen, Elisabeth

AU - Farooqi, I Sadaf

AU - McCarthy, Mark I

AU - Froguel, Philippe

AU - Meyre, David

AU - Hebebrand, Johannes

AU - Jarvelin, Marjo-Riitta

AU - Jaddoe, Vincent W V

AU - Smith, George Davey

AU - Hakonarson, Hakon

AU - Grant, Struan F A

AU - Boreham, Colin A G

AU - Neville, Charlotte E

AU - Moreno, Luis A

AU - Elliott, Paul

AU - Pouta, Anneli

AU - Hartikainen, Anna-Liisa

AU - Li, Mingyao

AU - Raitakari, Olli

AU - Lehtim├ñki, Terho

AU - Eriksson, Johan G

AU - Palotie, Aarno

AU - Dallongeville, Jean

AU - Das, Shikta

AU - Deloukas, Panos

AU - McMahon, George

AU - Ring, Susan M

AU - Kemp, John P

AU - Buxton, Jessica L

AU - Taal, H Rob

AU - Timpson, Nicholas J

AU - Bradfield, Jonathan P

AU - Scherag, Andr├®

AU - Lecoeur, Cecile

AU - Warrington, Nicole M

AU - Hypponen, Elina

AU - Holst, Claus

AU - Valcarcel, Beatriz

AU - Thiering, Elisabeth

AU - Salem, Rany M

AU - Schumacher, Fredrick R

AU - Cousminer, Diana L

AU - Sleiman, Patrick M A

AU - Zhao, Jianhua

AU - Berkowitz, Robert I

AU - Vimaleswaran, Karani S

AU - Jarick, Ivonne

AU - Pennell, Craig E

AU - Evans, David M

AU - St Pourcain, Beate

AU - Berry, Diane J

AU - Mook-Kanamori, Dennis O

AU - Hofman, Albert

AU - Rivadeneira, Fernando

AU - Uitterlinden, Andr├® G

AU - van Duijn, Cornelia M

AU - van der Valk, Ralf J P

AU - de Jongste, Johan C

AU - Postma, Dirkje S

AU - Boomsma, Dorret I

AU - Gauderman, W James

AU - Hassanein, Mohamed T

AU - Lindgren, Cecilia M

AU - M├ñgi, Reedik

PY - 2012/5/31

Y1 - 2012/5/31

N2 - 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 (ÔëÑ95th 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.

AB - 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 (ÔëÑ95th 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.

KW - Biological sciences

U2 - 10.1038/ng.2247

DO - 10.1038/ng.2247

M3 - Article

SN - 1061-4036

VL - 44

SP - 526

EP - 531

JO - Nature Genetics

JF - Nature Genetics

IS - 5

ER -

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

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