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 EvansB 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

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

322 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

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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

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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.",

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

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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

IS - 5

ER -