Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits
Suzanne Vogelezang(Erasmus MC), Jonathan P. Bradfield(Children's Hospital of Philadelphia), Tarunveer S. Ahluwalia(University of Copenhagen), John A. Curtin(Manchester Academic Health Science Centre), Timo A. Lakka(University of Eastern Finland), Niels Grarup(University of Copenhagen), Markus Scholz(Leipzig University), Peter J. van der Most(University Medical Center Groningen), Claire Monnereau(Erasmus MC), Evie Stergiakouli(University Of Bristol Dental Hospital), Anni Heiskala(University of Oulu), Momoko Horikoshi(Centre for Human Genetics), Iryna O. Fedko(Vrije Universiteit Amsterdam), Natàlia Vilor‐Tejedor(Pasqual Maragall Foundation), Diana L. Cousminer(Children's Hospital of Philadelphia), Marie Standl(Helmholtz Zentrum München), Carol A. Wang(University of Newcastle Australia), Jorma Viikari(University of Turku), Frank Geller(Statens Serum Institut), Carmen Íñiguez(Universitat Jaume I), Niina Pitkänen(University of Turku), Alessandra Chesi(Children's Hospital of Philadelphia), Jonas Bačelis(Sahlgrenska University Hospital), Loïc Yengo(The University of Queensland), Maties Torrent(Health Research Institute of the Balearic Islands), Ιωάννα Ντάλλα(Queen Mary University of London), Øyvind Helgeland(Norwegian Institute of Public Health), Saskia Selzam(King's College London), Judith M. Vonk(University Medical Center Groningen), Mohammed H. Zafarmand(GGD Amsterdam), Barbara Heude(Inserm), I. Sadaf Farooqi(University of Cambridge), Akram Alyass(Impact), Robin N. Beaumont(University of Exeter), Christian T. Have(University of Copenhagen), Peter Rzehak(Ludwig-Maximilians-Universität München), José Ramón Bilbao(University of the Basque Country), Theresia M. Schnurr(University of Copenhagen), Inês Barroso(University of Cambridge), Klaus Bønnelykke(University of Copenhagen), Lawrence J. Beilin(The University of Western Australia), Lisbeth Carstensen(Statens Serum Institut), Marie‐Aline Charles(Inserm), Bo Chawes(University of Copenhagen), Karine Clément(Inserm), Ricardo Closa‐Monasterolo(Institut de Recerca Biomèdica Catalunya Sud), Adnan Čustović(Imperial College London), Johan G. Eriksson(University of Helsinki), Joaquín Escribano(Institut de Recerca Biomèdica Catalunya Sud), Maria M. Groen‐Blokhuis(Vrije Universiteit Amsterdam), Veit Grote(Ludwig-Maximilians-Universität München), Dariusz Gruszfeld(Children's Memorial Health Institute), Håkon Håkonarson(Children's Hospital of Philadelphia), Torben Hansen(University of Copenhagen), Andrew T. Hattersley(University of Exeter), Mette Hollensted(University of Copenhagen), Jouke‐Jan Hottenga(Vrije Universiteit Amsterdam), Elina Hyppönen(University of South Australia), Stefan Johansson(Haukeland University Hospital), Raimo Joro(University of Eastern Finland), Mika Kähönen(Tampere University of Applied Sciences), Ville Karhunen(MRC Centre for Environment and Health), Wieland Kieß, Bridget Knight(University of Exeter), Berthold Koletzko(Ludwig-Maximilians-Universität München), Andreas Kühnapfel(Leipzig University), Kathrin Landgraf(IFB Adiposity Diseases), Jean‐Paul Langhendries(Centre Hospitalier Chrétien), Terho Lehtimäki(Tampere University), Jaakko T. Leinonen(University of Helsinki), Aihuali Li(Impact), Virpi Lindi(University of Eastern Finland), Estelle Lowry(Oulu University Hospital), Mariona Bustamante(Universitat Pompeu Fabra), Carolina Medina‐Gómez(Erasmus MC), Mads Melbye(Statens Serum Institut), Kim F. Michaelsen(University of Copenhagen), Camilla S. Morgen(University of Copenhagen), Trevor A. Mori(The University of Western Australia), Tenna Ruest Haarmark Nielsen(Hvidovre Hospital), Harri Niinikoski(University of Turku), Albertine J. Oldehinkel(University Medical Center Groningen), Katja Pahkala(University of Turku), Kalliope Panoutsopoulou(Wellcome Sanger Institute), Oluf Pedersen(University of Copenhagen), Craig E. Pennell(University of Newcastle Australia), Christopher Power(Great Ormond Street Hospital), Sijmen A. Reijneveld(University Medical Center Groningen), Fernando Rivadeneira(Erasmus MC), Angela Simpson(Manchester Academic Health Science Centre), Peter D. Sly(The University of Queensland), Jakob Stokholm(University of Copenhagen), Koon Teo(Impact), Elisabeth Thiering(Helmholtz Zentrum München), Nicholas J. Timpson(University of Bristol), André G. Uitterlinden(Erasmus MC), Catharina E. M. van Beijsterveldt(Vrije Universiteit Amsterdam), Barbera D. C. van Schaik(Amsterdam University Medical Centers), Marc Vaudel(Haukeland University Hospital), Elvira Verduci(University of Milan), Rebecca Vinding(University of Copenhagen), Mandy Vogel(IFB Adiposity Diseases), Eleftheria Zeggini(Wellcome Sanger Institute), Sylvain Sebért(Oulu University Hospital), Mads Vendelbo Lind(University of Copenhagen), Christopher D. Brown(University of Pennsylvania), Loreto Santa‐Marina(Biogipuzkoa Health Research Institute), Eva Reischl(Helmholtz Zentrum München), Christine Frithioff‐Bøjsøe(University of Copenhagen), David Meyre(Impact), Eleanor Wheeler(University of Cambridge), Ken K. Ong(University of Cambridge), Ellen A. Nøhr(University of Southern Denmark), Tanja G. M. Vrijkotte(GGD Amsterdam), Gerard H. Koppelman(University Medical Center Groningen), Robert Plomin(King's College London), Pål R. Njølstad(Broad Institute), George D. Dedoussis(Harokopio University of Athens), Philippe Froguel(Institut Pasteur de Lille), Thorkild I. A. Sørensen(University of Copenhagen), Bo Jacobsson(Norwegian Institute of Public Health), Rachel M. Freathy(University of Exeter), Babette S. Zemel(Children's Hospital of Philadelphia), Olli T. Raitakari(University of Turku), Martine Vrijheid(Universitat Pompeu Fabra), Bjarke Feenstra(Statens Serum Institut), Leo‐Pekka Lyytikäinen(Tampere University), Harold Snieder(University Medical Center Groningen), Holger Kirsten(Leipzig University), Patrick G. Holt(The Kids Research Institute Australia), Joachim Heinrich(The University of Melbourne), Elisabeth Widén(University of Helsinki), Jordi Sunyer(Universitat Pompeu Fabra), Dorret I. Boomsma(Vrije Universiteit Amsterdam), Marjo‐Riitta Järvelin(MRC Centre for Environment and Health), Antje Körner(IFB Adiposity Diseases), George Davey Smith(University of Bristol), Jens‐Christian Holm(University of Copenhagen), Mustafa Atalay(University of Eastern Finland), Clare Murray(Manchester Academic Health Science Centre), Hans Bisgaard(University of Copenhagen), Mark I. McCarthy(Centre for Human Genetics), Vincent W. V. Jaddoe(Erasmus MC), Struan F.A. Grant(Children's Hospital of Philadelphia), Janine F. Felix(Erasmus MC)
Cited by 231Open Access
Abstract
The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located near NEDD4L and SLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (Rg ranging from 0.11 to 0.76, P-values <0.002). A negative genetic correlation of childhood BMI with age at menarche was observed. Our results suggest that the biological processes underlying childhood BMI largely, but not completely, overlap with those underlying adult BMI. The well-known observational associations of BMI in childhood with cardio-metabolic diseases in adulthood may reflect partial genetic overlap, but in light of previous evidence, it is also likely that they are explained through phenotypic continuity of BMI from childhood into adulthood.
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