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

Suzanne Vogelezang; Jonathan P. Bradfield; Tarunveer S. Ahluwalia; John A. Curtin; Timo A. Lakka; Niels Grarup; Markus Scholz; Peter J. van der Most; Claire Monnereau; Evie Stergiakouli; Anni Heiskala; Momoko Horikoshi; Iryna O. Fedko; Natalia Vilor-Tejedor; Diana L. Cousminer; Marie Standl; Carol A. Wang; Jorma Viikari; Frank Geller; Carmen Íñiguez; Niina Pitkänen; Alessandra Chesi; Jonas Bacelis; Loic Yengo; Maties Torrent; Ioanna Ntalla; Øyvind Helgeland; Saskia Selzam; Judith M. Vonk; Mohammed H. Zafarmand; Barbara Heude; Ismaa Sadaf Farooqi; Akram Alyass; Robin N. Beaumont; Christian T. Have; Peter Rzehak; Jose Ramon Bilbao; Theresia M. Schnurr; Inês Barroso; Klaus Bønnelykke; Lawrence J. Beilin; Lisbeth Carstensen; Marie Aline Charles; Bo Chawes; Karine Clément; Johan G. Eriksson; Elina Hyppönen; Mika Kähönen; Terho Lehtimäki; Leo Pekka Lyytikäinen; Early Growth Genetics Consortium

doi:10.1371/journal.pgen.1008718

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

Suzanne Vogelezang, Jonathan P. Bradfield, Tarunveer S. Ahluwalia, John A. Curtin, Timo A. Lakka, Niels Grarup, Markus Scholz, Peter J. van der Most, Claire Monnereau, Evie Stergiakouli, Anni Heiskala, Momoko Horikoshi, Iryna O. Fedko, Natalia Vilor-Tejedor, Diana L. Cousminer, Marie Standl, Carol A. Wang, Jorma Viikari, Frank Geller, Carmen ÍñiguezNiina Pitkänen, Alessandra Chesi, Jonas Bacelis, Loic Yengo, Maties Torrent, Ioanna Ntalla, Øyvind Helgeland, Saskia Selzam, Judith M. Vonk, Mohammed H. Zafarmand, Barbara Heude, Ismaa Sadaf Farooqi, Akram Alyass, Robin N. Beaumont, Christian T. Have, Peter Rzehak, Jose Ramon Bilbao, Theresia M. Schnurr, Inês Barroso, Klaus Bønnelykke, Lawrence J. Beilin, Lisbeth Carstensen, Marie Aline Charles, Bo Chawes, Karine Clément, Johan G. Eriksson, Elina Hyppönen, Mika Kähönen, Terho Lehtimäki, Leo Pekka Lyytikäinen, Early Growth Genetics Consortium

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Tutkimustuotos: Artikkeli › Scientific › vertaisarvioitu

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Abstrakti

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 (R_g 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.

Alkuperäiskieli	Englanti
Artikkeli	e1008718
Julkaisu	PLoS Genetics
Vuosikerta	16
Numero	10
DOI - pysyväislinkit	https://doi.org/10.1371/journal.pgen.1008718
Tila	Julkaistu - 2020
OKM-julkaisutyyppi	A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä

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10.1371/journal.pgen.1008718Lisenssi: CC BY

novel_loci_for_2020
CC BY
Final published version, 1,51 MBLisenssi: CC BY

http://urn.fi/URN:NBN:fi:tuni-202012048518Lisenssi: CC BY

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Vogelezang, S., Bradfield, J. P., Ahluwalia, T. S., Curtin, J. A., Lakka, T. A., Grarup, N., Scholz, M., van der Most, P. J., Monnereau, C., Stergiakouli, E., Heiskala, A., Horikoshi, M., Fedko, I. O., Vilor-Tejedor, N., Cousminer, D. L., Standl, M., Wang, C. A., Viikari, J., Geller, F., ... Early Growth Genetics Consortium (2020). Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits. PLoS Genetics, 16(10), Artikkeli e1008718. https://doi.org/10.1371/journal.pgen.1008718

@article{86d150df4b514bb1b406292da29c0929,

title = "Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits",

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.",

author = "Suzanne Vogelezang and Bradfield, {Jonathan P.} and Ahluwalia, {Tarunveer S.} and Curtin, {John A.} and Lakka, {Timo A.} and Niels Grarup and Markus Scholz and {van der Most}, {Peter J.} and Claire Monnereau and Evie Stergiakouli and Anni Heiskala and Momoko Horikoshi and Fedko, {Iryna O.} and Natalia Vilor-Tejedor and Cousminer, {Diana L.} and Marie Standl and Wang, {Carol A.} and Jorma Viikari and Frank Geller and Carmen {\'I}{\~n}iguez and Niina Pitk{\"a}nen and Alessandra Chesi and Jonas Bacelis and Loic Yengo and Maties Torrent and Ioanna Ntalla and {\O}yvind Helgeland and Saskia Selzam and Vonk, {Judith M.} and Zafarmand, {Mohammed H.} and Barbara Heude and Farooqi, {Ismaa Sadaf} and Akram Alyass and Beaumont, {Robin N.} and Have, {Christian T.} and Peter Rzehak and Bilbao, {Jose Ramon} and Schnurr, {Theresia M.} and In{\^e}s Barroso and Klaus B{\o}nnelykke and Beilin, {Lawrence J.} and Lisbeth Carstensen and Charles, {Marie Aline} and Bo Chawes and Karine Cl{\'e}ment and Eriksson, {Johan G.} and Elina Hypp{\"o}nen and Mika K{\"a}h{\"o}nen and Terho Lehtim{\"a}ki and Lyytik{\"a}inen, {Leo Pekka} and {Early Growth Genetics Consortium}",

note = "Funding Information: Funding:CPreceivedfundingfromtheNational InstituteforHealthResearchBiomedicalResearch CentreatGreatOrmondStreetHospitalfor ChildrenNHSFoundationTrustandUniversity CollegeLondon.MMcCisaWellcomeSenior InvestigatorandanNIHRSeniorInvestigator. MMcCreceivedfundingfromWellcome(090532, 106130,098381,203141,212259),NIDDK(U01-DK105535),andNIHR(NF-SI-0617-10090).TGMV wassupportedbyZonMW(TOP40–00812–98– 11010).DLCwassupportedbytheAmerican DiabetesAssociationGrant1-17-PDF-077.SFAGis supportedbytheDanielB.BurkeChairforDiabetes ResearchandNIHGrantR01HD058886.NVTis fundedbyapre-doctoralgrantfromtheAg{\`e}nciade Gestio ´d{\textquoteright}AjutsUniversitarisideRecerca(2017 FI_B00636),GeneralitatdeCatalunya–Fons SocialEuropeu.BKreceivedpersonalfundingfrom theEuropeanResearchCouncilAdvancedGrant META-GROWTH(ERC-2012-AdG–no.322605). BFwassupportedbyanOakFoundation Fellowship.RMFandRNBaresupportedbySir HenryDaleFellowship(WellcomeTrustandRoyal Societygrant:WT104150).ATHissupportedbya WellcomeTrustSeniorInvestigatoraward(grant number098395/Z/12/Z).DMissupportedbya CanadaResearchChair.DLCwassupportedbythe AmericanDiabetesAssociationGrant1-17-PDF-077.JTLwassupportedbytheFinnishCultural Foundation.DIBreceivedaKNAWAcademy ProfessorAward(PAH/6635).MHreceivedPhD scholarshipfundingfromTARGET(http://target.ku. Publisher Copyright: {\textcopyright} 2020 Public Library of Science. All rights reserved. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",

year = "2020",

doi = "10.1371/journal.pgen.1008718",

language = "English",

volume = "16",

number = "10",

}

Vogelezang, S, Bradfield, JP, Ahluwalia, TS, Curtin, JA, Lakka, TA, Grarup, N, Scholz, M, van der Most, PJ, Monnereau, C, Stergiakouli, E, Heiskala, A, Horikoshi, M, Fedko, IO, Vilor-Tejedor, N, Cousminer, DL, Standl, M, Wang, CA, Viikari, J, Geller, F, Íñiguez, C, Pitkänen, N, Chesi, A, Bacelis, J, Yengo, L, Torrent, M, Ntalla, I, Helgeland, Ø, Selzam, S, Vonk, JM, Zafarmand, MH, Heude, B, Farooqi, IS, Alyass, A, Beaumont, RN, Have, CT, Rzehak, P, Bilbao, JR, Schnurr, TM, Barroso, I, Bønnelykke, K, Beilin, LJ, Carstensen, L, Charles, MA, Chawes, B, Clément, K, Eriksson, JG, Hyppönen, E, Kähönen, M , Lehtimäki, T , Lyytikäinen, LP & Early Growth Genetics Consortium 2020, 'Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits', PLoS Genetics, Vuosikerta 16, Nro 10, e1008718. https://doi.org/10.1371/journal.pgen.1008718

TY - JOUR

T1 - Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits

AU - Vogelezang, Suzanne

AU - Bradfield, Jonathan P.

AU - Ahluwalia, Tarunveer S.

AU - Curtin, John A.

AU - Lakka, Timo A.

AU - Grarup, Niels

AU - Scholz, Markus

AU - van der Most, Peter J.

AU - Monnereau, Claire

AU - Stergiakouli, Evie

AU - Heiskala, Anni

AU - Horikoshi, Momoko

AU - Fedko, Iryna O.

AU - Vilor-Tejedor, Natalia

AU - Cousminer, Diana L.

AU - Standl, Marie

AU - Wang, Carol A.

AU - Viikari, Jorma

AU - Geller, Frank

AU - Íñiguez, Carmen

AU - Pitkänen, Niina

AU - Chesi, Alessandra

AU - Bacelis, Jonas

AU - Yengo, Loic

AU - Torrent, Maties

AU - Ntalla, Ioanna

AU - Helgeland, Øyvind

AU - Selzam, Saskia

AU - Vonk, Judith M.

AU - Zafarmand, Mohammed H.

AU - Heude, Barbara

AU - Farooqi, Ismaa Sadaf

AU - Alyass, Akram

AU - Beaumont, Robin N.

AU - Have, Christian T.

AU - Rzehak, Peter

AU - Bilbao, Jose Ramon

AU - Schnurr, Theresia M.

AU - Barroso, Inês

AU - Bønnelykke, Klaus

AU - Beilin, Lawrence J.

AU - Carstensen, Lisbeth

AU - Charles, Marie Aline

AU - Chawes, Bo

AU - Clément, Karine

AU - Eriksson, Johan G.

AU - Hyppönen, Elina

AU - Kähönen, Mika

AU - Lehtimäki, Terho

AU - Lyytikäinen, Leo Pekka

AU - Early Growth Genetics Consortium

N1 - Funding Information: Funding:CPreceivedfundingfromtheNational InstituteforHealthResearchBiomedicalResearch CentreatGreatOrmondStreetHospitalfor ChildrenNHSFoundationTrustandUniversity CollegeLondon.MMcCisaWellcomeSenior InvestigatorandanNIHRSeniorInvestigator. MMcCreceivedfundingfromWellcome(090532, 106130,098381,203141,212259),NIDDK(U01-DK105535),andNIHR(NF-SI-0617-10090).TGMV wassupportedbyZonMW(TOP40–00812–98– 11010).DLCwassupportedbytheAmerican DiabetesAssociationGrant1-17-PDF-077.SFAGis supportedbytheDanielB.BurkeChairforDiabetes ResearchandNIHGrantR01HD058886.NVTis fundedbyapre-doctoralgrantfromtheAgènciade Gestio ´d’AjutsUniversitarisideRecerca(2017 FI_B00636),GeneralitatdeCatalunya–Fons SocialEuropeu.BKreceivedpersonalfundingfrom theEuropeanResearchCouncilAdvancedGrant META-GROWTH(ERC-2012-AdG–no.322605). BFwassupportedbyanOakFoundation Fellowship.RMFandRNBaresupportedbySir HenryDaleFellowship(WellcomeTrustandRoyal Societygrant:WT104150).ATHissupportedbya WellcomeTrustSeniorInvestigatoraward(grant number098395/Z/12/Z).DMissupportedbya CanadaResearchChair.DLCwassupportedbythe AmericanDiabetesAssociationGrant1-17-PDF-077.JTLwassupportedbytheFinnishCultural Foundation.DIBreceivedaKNAWAcademy ProfessorAward(PAH/6635).MHreceivedPhD scholarshipfundingfromTARGET(http://target.ku. Publisher Copyright: © 2020 Public Library of Science. All rights reserved. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2020

Y1 - 2020

N2 - 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.

AB - 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.

U2 - 10.1371/journal.pgen.1008718

DO - 10.1371/journal.pgen.1008718

M3 - Article

C2 - 33045005

AN - SCOPUS:85092931223

SN - 1553-7390

VL - 16

JO - PLoS Genetics

JF - PLoS Genetics

IS - 10

M1 - e1008718

ER -

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

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