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

JP Bradfield; Rob Taal; NJ Timpson; A Scherag; C Lecoeur; NM Warrington; E Hypponen; C Holst; B Valcarcel; E Thiering; RM Salem; FR Schumacher; DL Cousminer; PMA Sleiman; JH Zhao; RI Berkowitz; KS Vimaleswaran; I Jarick; CE Pennell; DM Evans; B St Pourcain; DJ Berry; Dennis Mook; Bert Hofman; Fernando Rivadeneira; André Uitterlinden; Cornelia Duijn; Ralf Valk; Johan Jongste; DS Postma; DI Boomsma; WJ Gauderman; MT Hassanein; CM Lindgren; R Magi; CAG Boreham; CE Neville; LA Moreno; P Elliott; A Pouta; AL Hartikainen; MY Li; O Raitakari; T Lehtimaki; JG Eriksson; A Palotie; J Dallongeville; Suman Das; P Deloukas; G McMahon; SM Ring; JP Kemp; JL Buxton; AIF Blakemore; M Bustamante; Monica Guxens Junyent; JN Hirschhorn; MW Gillman; E Kreiner-Moller; H Bisgaard; FD Gilliland; J (Joachim) Heinrich; E Wheeler; I Barroso; S O'Rahilly; A Meirhaeghe; TIA Sorensen; C Power; LJ Palmer; A Hinney; E Widen; IS Farooqi; MI McCarthy; P Froguel; D Meyre; J Hebebrand; MR Jarvelin; Vincent Jaddoe; GD Smith; H Hakonarson; SFA Grant

doi:10.1038/ng.2247

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

JP Bradfield
, Rob Taal
, NJ Timpson
, A Scherag
, C Lecoeur
, NM Warrington
, E Hypponen
, C Holst
, B Valcarcel
, E Thiering
, RM Salem
, FR Schumacher
, DL Cousminer
, PMA Sleiman
, JH Zhao
, RI Berkowitz
, KS Vimaleswaran
, I Jarick
, CE Pennell
, DM Evans

B St Pourcain, DJ Berry, Dennis Mook, Bert Hofman, Fernando Rivadeneira, André Uitterlinden, Cornelia Duijn, Ralf Valk, Johan Jongste, DS Postma, DI Boomsma, WJ Gauderman, MT Hassanein, CM Lindgren, R Magi, CAG Boreham, CE Neville, LA Moreno, P Elliott, A Pouta, AL Hartikainen, MY Li, O Raitakari, T Lehtimaki, JG Eriksson, A Palotie, J Dallongeville, Suman Das, P Deloukas, G McMahon, SM Ring, JP Kemp, JL Buxton, AIF Blakemore, M Bustamante, Monica Guxens Junyent, JN Hirschhorn, MW Gillman, E Kreiner-Moller, H Bisgaard, FD Gilliland, J (Joachim) Heinrich, E Wheeler, I Barroso, S O'Rahilly, A Meirhaeghe, TIA Sorensen, C Power, LJ Palmer, A Hinney, E Widen, IS Farooqi, MI McCarthy, P Froguel, D Meyre, J Hebebrand, MR Jarvelin, Vincent Jaddoe, GD Smith, H Hakonarson, SFA Grant

External organisation

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

342 Citations (Scopus)

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 x 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 x 10(-9); odds ratio (OR) = 1.22) and within HOXB5 at 17q21 (rs9299; P = 3.54 x 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 metaanalysis of adult BMI1.

Original language	Undefined/Unknown
Pages (from-to)	526-+
Journal	Nature Genetics
Volume	44
Issue number	5
DOIs	https://doi.org/10.1038/ng.2247
Publication status	Published - 2012

Research programs

EMC MM-01-39-09-A
EMC MM-04-54-08-A
EMC NIHES-01-64-01
EMC NIHES-01-64-02
EMC OR-01-54-02

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/ng.2247

http://hdl.handle.net/1765/57044

Cite this

Bradfield, JP., Taal, R., Timpson, NJ., Scherag, A., Lecoeur, C., Warrington, NM., Hypponen, E., Holst, C., Valcarcel, B., Thiering, E., Salem, RM., Schumacher, FR., Cousminer, DL., Sleiman, PMA., Zhao, JH., Berkowitz, RI., Vimaleswaran, KS., Jarick, I., Pennell, CE., ... Grant, SFA. (2012). A genome-wide association meta-analysis identifies new childhood obesity loci. Nature Genetics, 44(5), 526-+. https://doi.org/10.1038/ng.2247

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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 x 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 x 10(-9); odds ratio (OR) = 1.22) and within HOXB5 at 17q21 (rs9299; P = 3.54 x 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 metaanalysis of adult BMI1.",

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

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

AU - Bradfield, JP

AU - Taal, Rob

AU - Timpson, NJ

AU - Scherag, A

AU - Lecoeur, C

AU - Warrington, NM

AU - Hypponen, E

AU - Holst, C

AU - Valcarcel, B

AU - Thiering, E

AU - Salem, RM

AU - Schumacher, FR

AU - Cousminer, DL

AU - Sleiman, PMA

AU - Zhao, JH

AU - Berkowitz, RI

AU - Vimaleswaran, KS

AU - Jarick, I

AU - Pennell, CE

AU - Evans, DM

AU - St Pourcain, B

AU - Berry, DJ

AU - Mook, Dennis

AU - Hofman, Bert

AU - Rivadeneira, Fernando

AU - Uitterlinden, André

AU - Duijn, Cornelia

AU - Valk, Ralf

AU - Jongste, Johan

AU - Postma, DS

AU - Boomsma, DI

AU - Gauderman, WJ

AU - Hassanein, MT

AU - Lindgren, CM

AU - Magi, R

AU - Boreham, CAG

AU - Neville, CE

AU - Moreno, LA

AU - Elliott, P

AU - Pouta, A

AU - Hartikainen, AL

AU - Li, MY

AU - Raitakari, O

AU - Lehtimaki, T

AU - Eriksson, JG

AU - Palotie, A

AU - Dallongeville, J

AU - Das, Suman

AU - Deloukas, P

AU - McMahon, G

AU - Ring, SM

AU - Kemp, JP

AU - Buxton, JL

AU - Blakemore, AIF

AU - Bustamante, M

AU - Guxens Junyent, Monica

AU - Hirschhorn, JN

AU - Gillman, MW

AU - Kreiner-Moller, E

AU - Bisgaard, H

AU - Gilliland, FD

AU - Heinrich, J (Joachim)

AU - Wheeler, E

AU - Barroso, I

AU - O'Rahilly, S

AU - Meirhaeghe, A

AU - Sorensen, TIA

AU - Power, C

AU - Palmer, LJ

AU - Hinney, A

AU - Widen, E

AU - Farooqi, IS

AU - McCarthy, MI

AU - Froguel, P

AU - Meyre, D

AU - Hebebrand, J

AU - Jarvelin, MR

AU - Jaddoe, Vincent

AU - Smith, GD

AU - Hakonarson, H

AU - Grant, SFA

PY - 2012

Y1 - 2012

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 (>= 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 x 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 x 10(-9); odds ratio (OR) = 1.22) and within HOXB5 at 17q21 (rs9299; P = 3.54 x 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 metaanalysis of adult BMI1.

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 (>= 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 x 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 x 10(-9); odds ratio (OR) = 1.22) and within HOXB5 at 17q21 (rs9299; P = 3.54 x 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 metaanalysis of adult BMI1.

U2 - 10.1038/ng.2247

DO - 10.1038/ng.2247

M3 - Article

C2 - 22484627

SN - 1061-4036

VL - 44

SP - 526-+

JO - Nature Genetics

JF - Nature Genetics

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ER -