Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits

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...

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Autores: Vogelezang, Suzanne, Vilor Tejedor, Natàlia, 1988-, Bustamante Pineda, Mariona, Vrijheid, Martine, Sunyer Deu, Jordi, Felix, Janine Frédérique
Tipo de documento: artigo
Estado:Versão publicada
Data de publicação:2020
País:España
Recursos:Universitat Pompeu Fabra
Repositório:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/45783
Acesso em linha:http://hdl.handle.net/10230/45783
http://dx.doi.org/10.1371/journal.pgen.1008718
Access Level:Acceso aberto
Palavra-chave:Human genetics
Single nucleotide polymorphisms
Metaanalysis
Genetics of disease
Genome-wide association studies
Genetic loci
Body mass index
Adipose tissue
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spelling Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traitsVogelezang, SuzanneVilor Tejedor, Natàlia, 1988-Bustamante Pineda, MarionaVrijheid, MartineSunyer Deu, JordiFelix, Janine FrédériqueHuman geneticsSingle nucleotide polymorphismsMetaanalysisGenetics of diseaseGenome-wide association studiesGenetic lociBody mass indexAdipose tissueThe 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.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.Public Library of Science (PLoS)202020202020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/45783http://dx.doi.org/10.1371/journal.pgen.1008718reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésPLoS Genet. 2020; 16(10):e1008718info:eu-repo/grantAgreement/EC/FP7/322605info:eu-repo/grantAgreement/EC/H2020/648916info:eu-repo/grantAgreement/EC/FP7/279153© 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.http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/457832026-06-12T07:21:37Z
dc.title.none.fl_str_mv Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits
title Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits
spellingShingle Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits
Vogelezang, Suzanne
Human genetics
Single nucleotide polymorphisms
Metaanalysis
Genetics of disease
Genome-wide association studies
Genetic loci
Body mass index
Adipose tissue
title_short Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits
title_full Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits
title_fullStr Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits
title_full_unstemmed Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits
title_sort Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits
dc.creator.none.fl_str_mv Vogelezang, Suzanne
Vilor Tejedor, Natàlia, 1988-
Bustamante Pineda, Mariona
Vrijheid, Martine
Sunyer Deu, Jordi
Felix, Janine Frédérique
author Vogelezang, Suzanne
author_facet Vogelezang, Suzanne
Vilor Tejedor, Natàlia, 1988-
Bustamante Pineda, Mariona
Vrijheid, Martine
Sunyer Deu, Jordi
Felix, Janine Frédérique
author_role author
author2 Vilor Tejedor, Natàlia, 1988-
Bustamante Pineda, Mariona
Vrijheid, Martine
Sunyer Deu, Jordi
Felix, Janine Frédérique
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Human genetics
Single nucleotide polymorphisms
Metaanalysis
Genetics of disease
Genome-wide association studies
Genetic loci
Body mass index
Adipose tissue
topic Human genetics
Single nucleotide polymorphisms
Metaanalysis
Genetics of disease
Genome-wide association studies
Genetic loci
Body mass index
Adipose tissue
description 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.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/45783
http://dx.doi.org/10.1371/journal.pgen.1008718
url http://hdl.handle.net/10230/45783
http://dx.doi.org/10.1371/journal.pgen.1008718
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv PLoS Genet. 2020; 16(10):e1008718
info:eu-repo/grantAgreement/EC/FP7/322605
info:eu-repo/grantAgreement/EC/H2020/648916
info:eu-repo/grantAgreement/EC/FP7/279153
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science (PLoS)
publisher.none.fl_str_mv Public Library of Science (PLoS)
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
repository.name.fl_str_mv
repository.mail.fl_str_mv
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