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Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits |
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| Author: | Vogelezang, Suzanne1,2,3; Bradfield, Jonathan P.4,5; Ahluwalia, Tarunveer S.6,7,8; |
| Organizations: |
1Erasmus MC, Univ Med Ctr, Generat R Study Grp, Rotterdam, Netherlands. 2Erasmus MC, Univ Med Ctr, Dept Pediat, Rotterdam, Netherlands. 3Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
4Quantinuum Res LLC, San Diego, CA USA.
5Childrens Hosp Philadelphia, Div Human Genet, Ctr Appl Genom, Philadelphia, PA 19104 USA. 6Univ Copenhagen, Herlev & Gentofte Hosp, Copenhagen Prospect Studies Asthma Childhood, Copenhagen, Denmark. 7Steno Diabet Ctr Copenhagen, Gentofte, Denmark. 8Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metab Res, Copenhagen, Denmark. 9Univ Manchester, Div Infect Immun & Resp Med, Sch Biol Sci, Manchester Acad,Hlth Sci Ctr, Manchester, Lancs, England. 10Manchester Univ NHS Fdn Trust, Manchester, Lancs, England. 11Univ Eastern Finland, Inst Biomed, Physiol, Kuopio, Finland. 12Fdn Res Hlth Exercise & Nutr, Kuopio Res Inst Exercise Med, Kuopio, Finland. 13Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, Kuopio, Finland. 14Univ Leipzig, Inst Med Informat Stat & Epidemiol, Leipzig, Germany. 15Univ Leipzig, LIFE Res Ctr Civilizat Dis, Leipzig, Germany. 16Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands. 17Univ Bristol, MRC Integrat Epidemiol Unit, Bristol, Avon, England. 18Univ Bristol, Bristol Med Sch, Populat Hlth Sci, Bristol, Avon, England. 19Univ Bristol, Sch Oral & Dent Sci, Bristol, Avon, England. 20Univ Oulu, Ctr Life Course Hlth Res, Oulu, Finland. 21Univ Oxford, Wellcome Ctr Human Genet, Oxford, England. 22Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England. 23RIKEN Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan. 24Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands. 25ISGlobal, Barcelona, Spain. 26Barcelona Inst Sci & Technol, Ctr Genom Regulat CRG, Barcelona, Spain. 27Pasqual Maragall Fdn, BarcelonaBeta Brain Res Ctr BBRC, Barcelona, Spain. 28CIBER Epidemiol & Salud Publ CIBERESP, Madrid, Spain. 29Childrens Hosp Philadelphia, Div Human Genet, Philadelphia, PA 19104 USA. 30Univ Penn, Dept Genet, Philadelphia, PA 19104 USA. 31German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol, Neuherberg, Germany. 32Univ Newcastle, Sch Med & Publ Hlth, Fac Med & Hlth, Newcastle, NSW, Australia. 33Univ Turku, Dept Med, Turku, Finland. 34Turku Univ Hosp, Div Med, Turku, Finland. 35Statens Serum Inst, Dept Epidemiol Res, Copenhagen, Denmark. 36Univ Valencia, Dept Stat & Computat Res, Valencia, Spain. 37FISABIO Univ Jaume I Univ Valencia, Epidemiol & Environm Hlth Joint Res Unit, Valencia, Spain. 38Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland. 39Univ Turku, Ctr Populat Hlth Res, Turku, Finland. 40Turku Univ Hosp, Turku, Finland. 41Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Obstet & Gynecol, Gothenburg, Sweden. 42Sahlgrens Univ Hosp, Dept Obstet & Gynecol, Reg Vastra Gotaland, Gothenburg, Sweden. 43Univ Lille, Inst Pasteur Lille, CNRS, European Genom Inst Diabet,UMR 8199, Lille, France. 44Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia. 45Area Salut Menorca Ib Salut, Menorca, Spain. 46Inst Invest Sanitaria Illes Balears IdISBa, Palma De Mallorca, Spain. 47Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England. 48Univ Bergen, Dept Clin Sci, KG Jebsen Ctr Diabet Res, Bergen, Norway. 49Norwegian Inst Publ Hlth, Dept Genet & Bioinformat, Hlth Data & Digitalizat, Oslo, Norway. 50Kings Coll London, Inst Psychiat Psychol & Neurosci, Social Genet & Dev Psychiat Ctr, London, England. 51Univ Groningen, Univ Med Ctr Groningen, GRIAC Groningen Res Inst Asthma & COPD, Dept Epidemiol, Groningen, Netherlands. 52Univ Amsterdam, Amsterdam Publ Hlth Res Inst, Dept Publ Hlth, Amsterdam UMC, Amsterdam, Netherlands. 53Univ Amsterdam, Dept Obstet & Gynecol, Amsterdam UMC, Amsterdam, Netherlands. 54Univ Amsterdam, Amsterdam Publ Hlth Res Inst, Dept Clin Epidemiol Biostat & Bioinformat, Amsterdam UMC, Amsterdam, Netherlands. 55Univ Paris, CRESS, INSERM, INRA, Paris, France. 56Univ Cambridge, Metab Res Labs, Cambridge, England. 57Addenbrookes Hosp, NIHR Cambridge Biomed Res Ctr, Wellcome Trust MRC Inst Metab Sci, Cambridge, England. 58McMaster Univ, Dept Hlth Res Methods Evidence & Impact, Hamilton, New Zealand. 59Univ Exeter, Inst Biomed & Clin Sci, Coll Med & Hlth, Exeter, Devon, England. 60Ludwig Maximilians Univ Munchen LMU, Dr Von Hauner Childrens Hosp, Div Metab & Nutr Med, Munich, Germany. 61Univ Basque Country UPV EHU, Leioa, Spain. 62Biocrues Bizkaia Hlth Res Inst, Baracaldo, Spain. 63CIBER Diabet & Enfermedades Metab CIBERDEM, Madrid, Spain. 64Wellcome Sanger Inst, Cambridge, England. 65Univ Cambridge, MRC Epidemiol Unit, Cambridge, England. 66Univ Western Australia, Med Sch, Perth, WA, Australia. 67Sorbonne Univ, Pitie Salpetriere Hosp, AP HP, INSERM,Nutr & Obes Syst Approaches Res Unit, Paris, France. 68Univ Rovira & Virgili, Pediat Nutr & Dev Res Unit, IISPV, Reus, Spain. 69Imperial Coll London, Natl Heart & Lung Inst, London, England. 70Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland. 71Helsinki Univ Hosp, Helsinki, Finland. 72Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Obstet & Gynecol, Singapore, Singapore. 73Childrens Mem Hlth Inst, Neonatal Dept, Warsaw, Poland. 74Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA. 75Univ Exeter, Coll Med & Hlth, NIHR Exeter Clin Res Facil, Exeter, Devon, England. 76Royal Devon & Exeter NHS Fdn Trust, Exeter, Devon, England. 77Danish Diabet Acad, Odense, Denmark. 78Univ South Australia, Australian Ctr Precis Hlth, Canc Res Inst, Adelaide, SA, Australia. 79UCL, Populat Policy & Practice, UCL Inst Child Hlth, London, England. 80South Australian Hlth & Med Res Inst, Adelaide, SA, Australia. 81Haukeland Hosp, Dept Med Genet, Bergen, Norway. 82Tampere Univ Hosp, Dept Clin Physiol, Tampere, Finland. 83Tampere Univ, Fac Med & Hlth Technol, Dept Clin Physiol, Finnish Cardiovasc Res Ctr Tampere, Tampere, Finland. 84Imperial Coll, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England. 85Imperial Coll, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, London, England. 86Univ Leipzig, Univ Hosp Children & Adolescents, Ctr Pediat Res, Leipzig, Germany. 87Univ Leipzig, Integrated Res & Treatment Ctr IFB Adipos Dis, Leipzig, Germany. 88CHC Hlth Grp, Liege, Belgium. 89Fimlab Labs, Dept Clin Chem, Tampere, Finland. 90Tampere Univ, Fac Med & Hlth Technol, Dept Clin Chem, Finnish Cardiovasc Res Ctr Tampere, Tampere, Finland. 91Univ Helsinki, Inst Mol Med Finland, FIMM, Helsinki, Finland. 92Univ Eastern Finland Lib Kuopio, Kuopio, Finland. 93Oulu Univ Hosp, Bioctr Oulu, Oulu, Finland. 94Univ Pompeu Fabra UPF, Barcelona, Spain. 95Erasmus MC, Univ Med Ctr, Dept Internal Med, Rotterdam, Netherlands. 96Stanford Sch Med, Dept Med, Stanford, CA 94305 USA. 97Univ Copenhagen, Dept Nutr Exercise & Sports, Fac Sci, Copenhagen, Denmark. 98Univ Copenhagen, Epidemiol Sect, Dept Publ Hlth, Copenhagen, Denmark. 99Univ Southern Denmark, Natl Insitute Publ Hlth, Copenhagen, Denmark. 100Hvidovre Univ Hosp, Dept Pediat, Hvidovre, Denmark. 101Copenhagen Univ Hosp Holbaek, Dept Pediat, Childrens Obes Clin, Holbaek, Denmark. 102Univ Turku, Dept Physiol, Turku, Finland. 103Univ Turku, Dept Pediat, Turku, Finland. 104Univ Groningen, Univ Med Ctr, Interdisciplinary Ctr Psychopathol & Emot Regulat, Groningen, Netherlands. 105Univ Turku, Dept Phys Act & Hlth, Sports & Exercise Med Unit, Paavo Nurmi Ctr, Turku, Finland. 106Wellcome Trust Sanger Inst, Wellcome Genome Campus, Hinxton, Cambs, England. 107UCL, Populat Policy & Practice, UCL Great Ormond St Inst Child Hlth, London, England. 108Univ Groningen, Univ Med Ctr Groningen, Dept Hlth Sci, Groningen, Netherlands. 109Univ Queensland, Child Hlth Res Ctr, Brisbane, Qld, Australia. 110WHO, WHO Collaborating Ctr Childrens Hlth & Environm, Brisbane, Qld, Australia. 111McMaster Univ, Dept Med, Hamilton, ON, Canada. 112McMaster Univ, Dept Hlth Res Methods Evidence & Impact, Hamilton, ON, Canada. 113Netherlands Consortium Healthy Aging NCHA, Netherlands Genom Initiat NGI, Leiden, Netherlands. 114Univ Amsterdam, Bioinformat Lab, Dept Clin Epidemiol Biostat & Bioinformat, Amsterdam Publ Hlth Res Inst,Amsterdam UMC, Amsterdam, Netherlands. 115Univ Milan, San Paolo Hosp, Dept Pediat, Milan, Italy. 116German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Translat Genom, Neuherberg, Germany. 117Tech Univ Munich, TUM Sch Med, Munich, Germany. 118Klinikum Rechts Der Isar, Munich, Germany. 119Imperial Coll London, Sect Genom Common Dis, Dept Med, London, England. 120Univ Penn, Dept Genet, Perelman Sch Med, Philadelphia, PA 19104 USA. 121Consortium Biomed Res Epidemiol & Publ Hlth CIBER, Barcelona, Spain. 122Biodonostia Hlth Res Inst, San Sebastian, Spain. 123Subdirecc Salud Publ Gipuzkoa, San Sebastian, Spain. 124Helmholtz Zentrum Muenchen, Inst Epidemiol, Res Unit Mol Epidemiol, Munich, Germany. 125Univ Copenhagen, Fac Hlth & Med Sci, Copenhagen N, Denmark. 126Univ Cambridge, Addenbrookes Hosp, Med Res Council, Epidemiol Unit, Cambridge, England. 127Univ Cambridge, Addenbrookes Hosp, Dept Paediat, Cambridge, England. 128Univ Southern Denmark, Inst Clin Res, Res Unit Gynaecol & Obstet, Odense, Denmark. 129Univ Groningen, GRIAC Groningen Res Inst Asthma & COPD, Dept Pediat Pulmonol & Pediat Allergol, Univ Med Ctr Groningen,Beatrix Childrens Hosp, Groningen, Netherlands. 130Haukeland Hosp, Dept Pediat & Adolescents, Bergen, Norway. 131Broad Inst Harvard & MIT, Cambridge, MA USA. 132Harokopio Univ, Sch Hlth Sci & Educ, Dept Nutr & Dietet, Athens, Greece. 133Univ Bristol, Med Res Council, Integrat Epidemiol Unit, Bristol, Avon, England. 134Childrens Hosp Philadelphia, Div Gastroenterol Hepatol & Nutr, Philadelphia, PA 19104 USA. 135Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku, Finland. 136Tampere Univ Hosp, Dept Cardiol, Heart Ctr, Tampere, Finland. 137Univ Western Australia, Telethon Kids Inst, Perth, WA, Australia. 138Ludwig Maximilians Univ Munchen, Univ Hosp Munich, Inner City Clin, Inst & Outpatient Clin Occupat Social & Environm, Munich, Germany. 139Univ Melbourne, Melbourne Sch Populat & Global Hlth, Allergy & Lung Hlth Unit, Melbourne, Vic, Australia. 140Hosp del Mar Med Res Inst IMIM, Barcelona, Spain. 141Amsterdam Publ Hlth Res Inst, Amsterdam, Netherlands. 142Amsterdam Reprod & Dev Res Inst, Amsterdam, Netherlands. 143Churchill Hosp, Oxford Natl Inst Hlth Res NIHR, Biomed Res Ctr, Oxford, England. 144Childrens Hosp Philadelphia, Ctr Spatial & Funct Genom, Philadelphia, PA 19104 USA. |
| Format: | article |
| Version: | published version |
| Access: | open |
| Online Access: | PDF Full Text (PDF, 1.6 MB) |
| Persistent link: | http://urn.fi/urn:nbn:fi-fe202103106950 |
| Language: | English |
| Published: |
Public Library of Science,
2020
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| Publish Date: | 2021-03-10 |
| Description: |
AbstractThe 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. see all
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| Series: |
PLoS genetics |
| ISSN: | 1553-7390 |
| ISSN-E: | 1553-7404 |
| ISSN-L: | 1553-7390 |
| Volume: | 16 |
| Issue: | 10 |
| Article number: | e1008718 |
| DOI: | 10.1371/journal.pgen.1008718 |
| OADOI: | https://oadoi.org/10.1371/journal.pgen.1008718 |
| Type of Publication: |
A1 Journal article – refereed |
| Field of Science: |
3111 Biomedicine 3142 Public health care science, environmental and occupational health |
| Subjects: | |
| Funding: |
CP received funding from the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London. MMcC is a Wellcome Senior Investigator and an NIHR Senior Investigator. MMcC received funding from Wellcome (090532, 106130, 098381, 203141, 212259), NIDDK (U01-DK105535), and NIHR (NF-SI-0617-10090). TGMV was supported by ZonMW (TOP 40–00812–98–11010). DLC was supported by the American Diabetes Association Grant 1-17-PDF-077. SFAG is supported by the Daniel B. Burke Chair for Diabetes Research and NIH Grant R01 HD058886. NVT is funded by a pre-doctoral grant from the Agència de Gestió d’Ajuts Universitaris i de Recerca (2017 FI_B 00636), Generalitat de Catalunya – Fons Social Europeu. BK received personal funding from the European Research Council Advanced Grant META-GROWTH (ERC-2012-AdG – no. 322605). BF was supported by an Oak Foundation Fellowship. RMF and RNB are supported by Sir Henry Dale Fellowship (Wellcome Trust and Royal Society grant: WT104150). ATH is supported by a Wellcome Trust Senior Investigator award (grant number 098395/Z/12/Z). DM is supported by a Canada Research Chair. DLC was supported by the American Diabetes Association Grant 1-17-PDF-077. JTL was supported by the Finnish Cultural Foundation. DIB received a KNAW Academy Professor Award (PAH/6635). MH received PhD scholarship funding from TARGET (http://target.ku.dk), The Danish Diabetes Academy (http://danishdiabetesacademy.dk) and the Copenhagen Graduate School of Health and Medical Sciences. VWVJ received funding from the Netherlands Organization for Health Research and Development (VIDI 016.136.361) and the European Research Council (ERC-2014-CoG-648916). ISF was supported by the European Research Council, Wellcome Trust (098497/Z/12/Z), Medical Research Council (MRC_MC_UU_12012/5), the NIHR Cambridge Biomedical Research Centre, the Botnar Foundation, the Bernard Wolfe Health Neuroscience Endowment and the European Community’s Seventh Framework Programme (FP7/2007-2013) project Beta-JUDO n°279153. IB acknowledges funding from Wellcome (WT206194). ES works in a unit that receives funding from the University of Bristol and the UK Medical Research Council (MC_UU_00011/1, MC_UU_00011/3). GDS works in the Medical Research Council Integrative Epidemiology Unit at the University of Bristol, which is supported by the Medical Research Council (MC_UU_00011/1). KC received funds from the French National Agency of Research, F-CRIN/FORCE. All funding for the studies that provided the underlying data for this manuscript can be found in S1 Text. The funders had no role in study design, data collection and analysis, data interpretation, decision to publish, or preparation of the manuscript. |
| Copyright information: |
© 2020 Vogelezang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
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https://creativecommons.org/licenses/by/4.0/ |