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GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child, and adult BMI

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dc.contributor.author Couto Alves, Alexessander
dc.contributor.author Estivill, Xavier, 1955-
dc.contributor.author Sunyer Deu, Jordi
dc.contributor.author Early Growth Genetics (EGG) Consortium
dc.date.accessioned 2019-11-08T08:58:50Z
dc.date.available 2019-11-08T08:58:50Z
dc.date.issued 2019
dc.identifier.citation Couto Alves A, De Silva NMG, Karhunen V, Sovio U, Das S, Taal HR et al. GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child, and adult BMI. Sci Adv. 2019;5(9):eaaw3095. DOI: 10.1126/sciadv.aaw3095
dc.identifier.issn 2375-2548
dc.identifier.uri http://hdl.handle.net/10230/42795
dc.description.abstract Early childhood growth patterns are associated with adult health, yet the genetic factors and the developmental stages involved are not fully understood. Here, we combine genome-wide association studies with modeling of longitudinal growth traits to study the genetics of infant and child growth, followed by functional, pathway, genetic correlation, risk score, and colocalization analyses to determine how developmental timings, molecular pathways, and genetic determinants of these traits overlap with those of adult health. We found a robust overlap between the genetics of child and adult body mass index (BMI), with variants associated with adult BMI acting as early as 4 to 6 years old. However, we demonstrated a completely distinct genetic makeup for peak BMI during infancy, influenced by variation at the LEPR/LEPROT locus. These findings suggest that different genetic factors control infant and child BMI. In light of the obesity epidemic, these findings are important to inform the timing and targets of prevention strategies.
dc.description.sponsorship All the authors acknowledge the following sponsors for support: UK Medical Research Council and Wellcome Trust (grant reference 102215/2/13/2); NIH grant R01 HD056465; Danish National Research Foundation; NIH Genes, Environment and Health Initiative (GEI; U01HG004423); NIH GEI (U01HG004438); Lundbeck Foundation (R19-A2059); Danish Medical Research Council (09-065592); French Ministry of Research; INSERM; South West NHS Research and Development; Exeter NHS Research and Development; Netherlands Organization for Health Research and Development (VIDI 016. 136. 361); European Union’s Horizon 2020 research and innovation programme under grant agreement nos. 633595 (DynaHEALTH), 733206 (LIFECYCLE), and 721567 (CAPICE); European Research Council (ERC consolidator grant, ERC-2014-CoG-648916); Academy of Finland (project grants 209072 and 129255); British Heart Foundation and Academy of Finland (grants 134839 and 129287); National Public Health Institute, Helsinki, Finland; World Cancer Research Fund (WCRF UK) and World Cancer Research Fund International (2017/1641); Wellcome Trust (WT205915); European Commission under the Marie Curie Intra-European Fellowship (project MARVEL, PIEF-GA-2013-626461); Instituto de Salud Carlos III (CB06/02/0041, FIS PI041436, PI081151, PI041705, and PS09/00432 and FIS-FEDER 03/1615, 04/1509, 04/1112, 04/1931, 05/1079, 05/1052, 06/1213, 07/0314, and 09/02647); Spanish Ministry of Science and Innovation (SAF2008-00357); European Commission (ENGAGE project and grant agreement HEALTH-F4-2007-201413); Fundació La Marató de TV3; Generalitat de Catalunya-CIRIT 1999SGR 00241; Federal Ministry for Environment (IUF Düsseldorf, FKZ 20462296); National Health and Medical Research Council of Australia (grant IDs 403981 and 003209); Canadian Institutes of Health Research (grant ID MOP-82893); Royal Society of New Zealand Marsden Fund (grant 16-UOO-072); Academy of Finland (project grants 104781, 120315, 129269, 1114194, Center of Excellence in Complex Disease Genetics, and SALVE); University Hospital Oulu; Biocenter; University of Oulu, Finland (75617); European Commission (EURO-BLCS, Framework 5 award QLG1-CT-2000-01643); NHLBI grant 5R01HL087679-02 through the STAMPEED program (1RL1MH083268-01); NIH/NIMH (5R01MH63706:02); Medical Research Council, United Kingdom (G0500539 and G0600705, PrevMetSyn/SALVE, MR/M013138, G0802782); Wellcome Trust (project grant GR069224); and EU Framework Programme 7 EurHEALTHAgeing 277849. This research was conducted using the UK Biobank Resource.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher American Association for the Advancement of Science (AAAS)
dc.relation.ispartof Science Advances. 2019;5(9):eaaw3095
dc.rights Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.title GWAS on longitudinal growth traits reveals different genetic factors influencing infant, child, and adult BMI
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1126/sciadv.aaw3095
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/633595
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/733206
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/721567
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/648916
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2008-00357
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/277849
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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