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; Hans Bisgaard; Thorkild I A Sørensen; Early Growth Genetics Consortium

doi:10.1038/ng.2247

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 EvansBeate 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, Hans Bisgaard, Thorkild I A Sørensen, Early Growth Genetics Consortium

240 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 × 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
Journal	Nature Genetics
Volume	44
Issue number	5
Pages (from-to)	526-31
Number of pages	6
ISSN	1061-4036
DOIs	https://doi.org/10.1038/ng.2247
Publication status	Published - May 2012

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Bradfield, J. P., Taal, H. R., Timpson, N. J., Scherag, A., Lecoeur, C., Warrington, N. M., Hypponen, E., Holst, C., Valcarcel, B., Thiering, E., Salem, R. M., Schumacher, F. R., Cousminer, D. L., Sleiman, P. M. A., Zhao, J., Berkowitz, R. I., Vimaleswaran, K. S., Jarick, I., Pennell, C. E., ... Early Growth Genetics Consortium (2012). A genome-wide association meta-analysis identifies new childhood obesity loci. Nature Genetics, 44(5), 526-31. https://doi.org/10.1038/ng.2247

Bradfield, JP, Taal, HR, 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, 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, Mägi, R, Boreham, CAG, Neville, CE, Moreno, LA, Elliott, P, Pouta, A, Hartikainen, A-L, Li, M, Raitakari, O, Lehtimäki, T, Eriksson, JG, Palotie, A, Dallongeville, J, Das, S, Bisgaard, H, Sørensen, TIA & Early Growth Genetics Consortium 2012, 'A genome-wide association meta-analysis identifies new childhood obesity loci', Nature Genetics, vol. 44, no. 5, pp. 526-31. https://doi.org/10.1038/ng.2247

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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 (≥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.",

author = "Bradfield, {Jonathan P} and Taal, {H Rob} and Timpson, {Nicholas J} and Andr{\'e} 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{\'e} 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{\"a}gi 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{\"a}ki and Eriksson, {Johan G} and Aarno Palotie and Jean Dallongeville and Shikta Das and Hans Bisgaard and S{\o}rensen, {Thorkild I A} and S{\o}rensen, {Thorkild I.A.}",

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

AU - Bradfield, Jonathan P

AU - Taal, H Rob

AU - Timpson, Nicholas J

AU - Scherag, André

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, André 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 - Mägi, Reedik

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 - Lehtimäki, Terho

AU - Eriksson, Johan G

AU - Palotie, Aarno

AU - Dallongeville, Jean

AU - Das, Shikta

AU - Bisgaard, Hans

AU - Sørensen, Thorkild I A

AU - Early Growth Genetics Consortium

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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 × 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 (≥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.

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DO - 10.1038/ng.2247

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JO - Nature: New biology

JF - Nature: New biology

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

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