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PMID: 22484627 Published · ppublish English Comparative Study Journal Article Meta-Analysis Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

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

Nature genetics ·Vol. 44 ·No. 5 ·2012-05-00 ·Pages 526-31

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 PM, 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 RJ, de Jongste JC, Postma DS, Boomsma DI, Gauderman WJ, Hassanein MT, Lindgren CM, Mägi R, Boreham CA, Neville CE, Moreno LA, Elliott P, Pouta A, Hartikainen AL, Li M, Raitakari O, Lehtimäki T, Eriksson JG, Palotie A, Dallongeville J, Das S, Deloukas P, McMahon G, Ring SM, Kemp JP, Buxton JL, Blakemore AI, 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 TI, Power C, Palmer LJ, Hinney A, Widen E, Farooqi IS, McCarthy MI, Froguel P, Meyre D, Hebebrand J, Jarvelin MR, Jaddoe VW, Smith GD, Hakonarson H, Grant SF, Early Growth Genetics Consortium

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).

MeSH Terms
Adolescent Adult Body Mass Index Case-Control Studies Genetic Loci Genetic Markers Genetic Predisposition to Disease Genome-Wide Association Study Humans Obesity/genetics Polymorphism, Single Nucleotide/genetics Young Adult
Chemicals
Genetic Markers
Authors & Affiliations
82 authors, click to expand affiliations / ORCID
Bradfield Jonathan P
Center for Applied Genomics, Abramson Research Center, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Taal H Rob
Timpson Nicholas J
Scherag André
Lecoeur Cecile
Warrington Nicole M
Hypponen Elina
Holst Claus
Valcarcel Beatriz
Thiering Elisabeth
Salem Rany M
Schumacher Fredrick R
Cousminer Diana L
Sleiman Patrick M A
Zhao Jianhua
Berkowitz Robert I
Vimaleswaran Karani S
Jarick Ivonne
Pennell Craig E
Evans David M
St Pourcain Beate
Berry Diane J
Mook-Kanamori Dennis O
Hofman Albert
Rivadeneira Fernando
Uitterlinden André G
van Duijn Cornelia M
van der Valk Ralf J P
de Jongste Johan C
Postma Dirkje S
Boomsma Dorret I
Gauderman W James
Hassanein Mohamed T
Lindgren Cecilia M
Mägi Reedik
Boreham Colin A G
Neville Charlotte E
Moreno Luis A
Elliott Paul
Pouta Anneli
Hartikainen Anna-Liisa
Li Mingyao
Raitakari Olli
Lehtimäki Terho
Eriksson Johan G
Palotie Aarno
Dallongeville Jean
Das Shikta
Deloukas Panos
McMahon George
Ring Susan M
Kemp John P
Buxton Jessica L
Blakemore Alexandra I F
Bustamante Mariona
Guxens Mònica
Hirschhorn Joel N
Gillman Matthew W
Kreiner-Møller Eskil
Bisgaard Hans
Gilliland Frank D
Heinrich Joachim
Wheeler Eleanor
Barroso Inês
O'Rahilly Stephen
Meirhaeghe Aline
Sørensen Thorkild I A
Power Chris
Palmer Lyle J
Hinney Anke
Widen Elisabeth
Farooqi I Sadaf
McCarthy Mark I
Froguel Philippe
Meyre David
Hebebrand Johannes
Jarvelin Marjo-Riitta
Jaddoe Vincent W V
Smith George Davey
Hakonarson Hakon
Grant Struan F A
Early Growth Genetics Consortium
Investigators
112 investigators, click to expand
Adair Linda S
Ang Wei
Atalay Mustafa
van Beijsterveldt Toos
Bergen Nienke
Benke Kelly
Berry Diane
Bradfield Jonathan
Bustamente Mariona
Charoen Pimphen
Coin Lachlan
Cousminer Diana
Das Shikta
Davis Oliver S P
Elliott Paul
Evans Dave M
Feenstra Bjarke
Flexeder Claudia
Frayling Tim
Freathy Rachel
Gaillard Romy
Geller Frank
Groen-Blokhuis Maria
Goh Liang-Kee
Guxens Mònica
Haworth Claire M A
Hadley Dexter
Hedebrand Johannes
Hinney Anke
Hirschhorn Joel N
Holloway John W
Holst Claus
Hottenga Jouke Jan
Horikoshi Momoko
Huikari Ville
Hypponen Elina
Iñiguez Carmen
Kaakinen Marika
Kilpeläinen Tuomas O
Kirin Mirna
Kowgier Mattew
Lakka Hanna-Maaria
Lange Leslie A
Lawlor Debbie A
Lehtimäki Terho
Lewin Alex
Lindgren Cecilia
Lindi Virpi
Mägi Reedik
Marsh Julie
Middeldorp Christel
Millwood Iona
Mook-Kanamori Dennis O
Murray Jeffrey C
Nivard Michel
Nohr Ellen Aagaard
Ntalla Ioanna
Oken Emily
O'Reilly Paul
Palmer Lyle
Panoutsopoulou Kalliope
Pararajasingham Jennifer
Prokopenko Inga
Rodriguez Alina
Salem Rany M
Sebert Sylvain
Siitonen Niina
Sovio Ulla
St Pourcain Beate
Strachan David P
Sunyer Jordi
Taal H Rob
Teo Yik-Ying
Thiering Elisabeth
Tiesler Carla
Uitterlinden Andre G
Valcárcel Beatriz
Warrington Nicole
White Scott
Willemsen Gonneke
Yaghootkar Hanieh
Zeggini Eleftheria
Boomsma Dorret I
Cooper Cyrus
Estivill Xavier
Gillman Matthew
Grant Struan F A
Hakonarson Hakon
Hattersley Andrew T
Heinrich Joachim
Hocher Berthold
Jaddoe Vincent W V
Jarvelin Marjo-Riitta
Lakka Timo A
McCarthy Mark I
Melbye Mads
Mohlke Karen L
Dedoussis George V
Ong Ken K
Pearson Ewan R
Pennell Craig E
Price Thomas S
Power Chris
Raitakari Olli T
Saw Seang-Mei
Scherag Andre
Simell Olli
Sørensen Thorkild I A
Sunyer Jordi
Timpson Nicholas J
Widen Elisabeth
Wilson James F
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Article Info
Journal
Nature genetics
Abbr.
Nat Genet
ISSN
1546-1718
DOI
10.1038/ng.2247
Published
2012-05-00
Pages
526-31
Language
English
Region
United States
NLM ID
9216904
PMCID
PMC3370100
Subset
IM
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External Links
PubMed source DOI: 10.1038/ng.2247 PMC Full Text View journal details
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