Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index

Janine F. Felix; Jonathan P. Bradfield; Claire Monnereau; Ralf J.P. Van Der Valk; Evie Stergiakouli; Alessandra Chesi; Romy Gaillard; Bjarke Feenstra; Elisabeth Thiering; Eskil Kreiner-Møller; Anubha Mahajan; Pitkänen Niina Pitkänen; Raimo Joro; Alana Cavadino; Ville Huikari; Steve Franks; Maria M. Groen-Blokhuis; Diana L. Cousminer; Julie A. Marsh; Terho Lehtimäki; John A. Curtin; Jesus Vioque; Tarunveer S. Ahluwalia; Ronny Myhre; Thomas S. Price; Vilor-Tejedor Natalia Vilor-Tejedor; Loïc Yengo; Niels Grarup; Ioanna Ntalla; Wei Ang; Mustafa Atalay; Hans Bisgaard; Alexandra I. Blakemore; Amelie Bonnefond; Lisbeth Carstensen; Johan Eriksson; Claudia Flexeder; Lude Franke; Frank Geller; Mandy Geserick; Anna Liisa Hartikainen; Claire M.A. Haworth; Joel N. Hirschhorn; Albert Hofman; Jens Christian Holm; Momoko Horikoshi; Jouke Jan Hottenga; Jinyan Huang; Haja N. Kadarmideen; Mika Kähönen; Wieland Kiess; Hanna Maaria Lakka; Timo A. Lakka; Alexandra M. Lewin; Liming Liang; Leo Pekka Lyytikäinen; Baoshan Ma; Per Magnus; Shana E. McCormack; George McMahon; Frank D. Mentch; Christel M. Middeldorp; Clare S. Murray; Katja Pahkala; Tune H. Pers; Roland Pfäffle; Dirkje S. Postma; Christine Power; Angela Simpson; Verena Sengpiel; Carla M.T. Tiesler; Maties Torrent; André G. Uitterlinden; Joyce B. Van Meurs; Rebecca Vinding; Johannes Waage; Jane Wardle; Eleftheria Zeggini; Babette S. Zemel; George V. Dedoussis; Oluf Pedersen; Philippe Froguel; Jordi Sunyer; Robert Plomin; Bo Jacobsson; Torben Hansen; Juan R. Gonzalez; Adnan Custovic; Olli T. Raitakari; Craig E. Pennell; Widén Elisabeth Widén; Dorret I. Boomsma; Gerard H. Koppelman; Sylvain Sebert; Marjo Riitta Järvelin; Elina Hyppönen; Mark I. McCarthy; Virpi Lindi; Niinikoski Harri; Antje Körner; Klaus Bønnelykke; Joachim Heinrich; Mads Melbye; Fernando Rivadeneira; Hakon Hakonarson; Susan M. Ring; George Davey Smith; Thorkild I.A. Sørensen; Nicholas J. Timpson; Struan F.A. Grant; Vincent W.V. Jaddoe; Heidi J. Kalkwarf; Joan M. Lappe; Vicente Gilsanz; Sharon E. Oberfield; John A. Shepherd; Andrea Kelly

doi:10.1093/hmg/ddv472

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Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index

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Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index

Janine F. Felix, Jonathan P. Bradfield, Claire Monnereau, Ralf J.P. Van Der Valk, Evie Stergiakouli, Alessandra Chesi, Romy Gaillard, Bjarke Feenstra, Elisabeth Thiering, Eskil Kreiner-Møller, …

Human Molecular Genetics, Vol.25(2), pp.389-403

01/15/2016

DOI: https://doi.org/10.1093/hmg/ddv472

PMID: 26604143

Abstract

Molecular Biology

Genetics

Genetics(clinical)

A large number of genetic loci are associated with adult body mass index. However, the genetics of childhood body mass index are largely unknown.We performed a meta-analysis of genome-wide association studies of childhood body mass index, using sex- and age-adjusted standard deviation scores.We included 35 668 children from 20 studies in the discovery phase and 11 873 children from 13 studies in the replication phase. In total, 15 loci reached genome-wide significance (P-value <5 × 10-8) in the joint discovery and replication analysis, of which 12 are previously identified loci in or close to ADCY3, GNPDA2, TMEM18, SEC16B, FAIM2, FTO, TFAP2B, TNNI3K, MC4R, GPR61, LMX1B and OLFM4 associated with adult body mass index or childhood obesity. We identified three novel loci: rs13253111 near ELP3, rs8092503 near RAB27B and rs13387838 near ADAM23. Per additional risk allele, body mass index increased 0.04 Standard Deviation Score (SDS) [Standard Error (SE) 0.007], 0.05 SDS (SE 0.008) and 0.14 SDS (SE 0.025), for rs13253111, rs8092503 and rs13387838, respectively. A genetic risk score combining all 15 SNPs showed that each additional average risk allele was associated with a 0.073 SDS (SE 0.011, P-value = 3.12 × 10-10) increase in childhood body mass index in a population of 1955 children. This risk score explained 2% of the variance in childhood body mass index. This study highlights the shared genetic background between childhood and adult body mass index and adds three novel loci. These loci likely represent age-related differences in strength of the associations with body mass index.

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Title: Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index
Creators: Janine F. Felix (Author) - Erasmus University Rotterdam
Jonathan P. Bradfield (Author) - University of Pennsylvania
Claire Monnereau (Author) - Erasmus University Rotterdam
Ralf J.P. Van Der Valk (Author) - GRIAC (Groningen Research Institute for Asthma and COPD)
Evie Stergiakouli (Author) - University of Bristol
Alessandra Chesi (Author) - University of Pennsylvania
Romy Gaillard (Author) - Erasmus University Rotterdam
Bjarke Feenstra (Author) - Statens Serum Institut
Elisabeth Thiering (Author) - Helmholtz Zentrum München - German Research Center for Environmental Health;Ludwig Maximilian University of Munich
Eskil Kreiner-Møller (Author) - University of Copenhagen
Anubha Mahajan (Author) - University of Oxford
Pitkänen Niina Pitkänen (Author) - University of Turku;University of Eastern Finland
Raimo Joro (Author) - University of Eastern Finland
Alana Cavadino (Author) - Queen Mary University of London;University College London
Ville Huikari (Author) - University of Oulu
Steve Franks (Author) - Imperial College London
Maria M. Groen-Blokhuis (Author) - University of Amsterdam
Diana L. Cousminer (Author) - University of Helsinki
Julie A. Marsh (Author) - University of Western Australia
Terho Lehtimäki (Author) - Fimlab Laboratories;Tampere University
John A. Curtin (Author) - University of Manchester;Manchester University NHS Foundation Trust
Jesus Vioque (Author) - Miguel Hernández University;Instituto de Salud Carlos III
Tarunveer S. Ahluwalia (Author) - University of Copenhagen;Novo Nordisk Foundation
Ronny Myhre (Author) - Norwegian Institute of Public Health
Thomas S. Price (Author) - University of Pennsylvania
Vilor-Tejedor Natalia Vilor-Tejedor (Author) - Instituto de Salud Carlos III;Barcelona Institute for Global Health;Pompeu Fabra University
Loïc Yengo (Author) - Institut Pasteur de Lille;Institut national de la santé et de la recherche médicale
Niels Grarup (Author) - University of Copenhagen
Ioanna Ntalla (Author) - University of Leicester;Harokopio University
Wei Ang (Author) - University of Western Australia
Mustafa Atalay (Author) - University of Eastern Finland
Hans Bisgaard (Author) - University of Copenhagen
Alexandra I. Blakemore (Author) - Imperial College London
Amelie Bonnefond (Author) - Institut Pasteur de Lille;Institut national de la santé et de la recherche médicale
Lisbeth Carstensen (Author) - Statens Serum Institut
Johan Eriksson (Author) - National Institute for Health and Welfare
Claudia Flexeder (Author) - Helmholtz Zentrum München - German Research Center for Environmental Health
Lude Franke (Author) - University of Groningen
Frank Geller (Author) - Statens Serum Institut
Mandy Geserick (Author) - Leipzig University
Anna Liisa Hartikainen (Author) - University of Oulu
Claire M.A. Haworth (Author) - University of Warwick
Joel N. Hirschhorn (Author) - Harvard University;Broad Institute
Albert Hofman (Author) - Erasmus University Rotterdam
Jens Christian Holm (Author) - University of Copenhagen
Momoko Horikoshi (Author) - University of Oxford
Jouke Jan Hottenga (Author) - University of Amsterdam
Jinyan Huang (Author) - Shanghai Jiao Tong University
Haja N. Kadarmideen (Author) - University of Copenhagen
Mika Kähönen (Author) - Tampere University
Wieland Kiess (Author) - Leipzig University
Hanna Maaria Lakka (Author) - University of Eastern Finland
Timo A. Lakka (Author) - University of Eastern Finland
Alexandra M. Lewin (Author) - Imperial College
Liming Liang (Author) - Harvard University
Leo Pekka Lyytikäinen (Author) - Fimlab Laboratories;Tampere University
Baoshan Ma (Author) - Dalian Maritime University
Per Magnus (Author) - Norwegian Institute of Public Health
Shana E. McCormack (Author) - University of Pennsylvania
George McMahon (Author) - University of Bristol
Frank D. Mentch (Author) - University of Pennsylvania
Christel M. Middeldorp (Author) - University of Amsterdam
Clare S. Murray (Author) - University of Manchester;Manchester University NHS Foundation Trust
Katja Pahkala (Author) - University of Turku
Tune H. Pers (Author) - Harvard University;Broad Institute
Roland Pfäffle (Author) - Leipzig University
Dirkje S. Postma (Author) - GRIAC (Groningen Research Institute for Asthma and COPD)
Christine Power (Author) - University College London
Angela Simpson (Author) - University of Manchester
Verena Sengpiel (Author) - University of Gothenburg
Carla M.T. Tiesler (Author) - Helmholtz Zentrum München - German Research Center for Environmental Health;Ludwig Maximilian University of Munich
Maties Torrent (Author) - Instituto de Salud Carlos III;Area de Salut de Menorca
André G. Uitterlinden (Author) - Erasmus University Rotterdam
Joyce B. Van Meurs (Author) - Erasmus University Rotterdam
Rebecca Vinding (Author) - University of Copenhagen
Johannes Waage (Author) - University of Copenhagen
Jane Wardle (Author) - University College London
Eleftheria Zeggini (Author) - Wellcome Sanger Institute
Babette S. Zemel (Author) - University of Pennsylvania
George V. Dedoussis (Author) - Harokopio University
Oluf Pedersen (Author) - University of Copenhagen
Philippe Froguel (Author) - Institut Pasteur de Lille;Hammersmith Hospital
Jordi Sunyer (Author) - Instituto de Salud Carlos III;Barcelona Institute for Global Health;Pompeu Fabra University
Robert Plomin (Author) - Medical Research Council
Bo Jacobsson (Author) - Norwegian Institute of Public Health;University of Gothenburg
Torben Hansen (Author) - University of Copenhagen
Juan R. Gonzalez (Author) - Instituto de Salud Carlos III;Barcelona Institute for Global Health;Pompeu Fabra University
Adnan Custovic (Author) - University of Manchester;Manchester University NHS Foundation Trust
Olli T. Raitakari (Author) - University of Turku
Craig E. Pennell (Author) - University of Western Australia
Widén Elisabeth Widén (Author) - University of Helsinki
Dorret I. Boomsma (Author) - University of Amsterdam
Gerard H. Koppelman (Author) - University of Groningen
Sylvain Sebert (Author) - University of Oulu
Marjo Riitta Järvelin (Author) - University of Oulu;Imperial College;National Institute for Health and Welfare
Elina Hyppönen (Author) - University College London;University of South Australia;South Australian Health And Medical Research Institute
Mark I. McCarthy (Author) - University of Oxford;Churchill Hospital
Virpi Lindi (Author) - University of Eastern Finland
Niinikoski Harri (Author) - University of Turku
Antje Körner (Author) - Leipzig University
Klaus Bønnelykke (Author) - University of Copenhagen
Joachim Heinrich (Author) - Helmholtz Zentrum München - German Research Center for Environmental Health
Mads Melbye (Author) - Statens Serum Institut;Stanford University
Fernando Rivadeneira (Author) - Erasmus University Rotterdam
Hakon Hakonarson (Author) - University of Pennsylvania;University of Gothenburg
Susan M. Ring (Author) - University of Bristol
George Davey Smith (Author) - University of Bristol
Thorkild I.A. Sørensen (Author) - University of Bristol;University of Copenhagen
Nicholas J. Timpson (Author) - University of Bristol
Struan F.A. Grant (Author) - University of Pennsylvania
Vincent W.V. Jaddoe (Author) - Erasmus University Rotterdam
Heidi J. Kalkwarf (Author) - Cincinnati Children's Hospital Medical Center
Joan M. Lappe (Author) - College of Nursing
Vicente Gilsanz (Author) - University of Southern California
Sharon E. Oberfield (Author) - Columbia University
John A. Shepherd (Author) - University of Southern California
Andrea Kelly (Author) - University of Pennsylvania
Publication Details: Human Molecular Genetics, Vol.25(2), pp.389-403
Series: 25
Number of pages: 15
Identifiers: 991005929695302656
Academic Unit: College of Nursing
Language: English
Resource Type: Journal article