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

Early Growth Genetics Consortium

doi:10.1371/journal.pgen.1008718

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

Early Growth Genetics Consortium

Erasmus MC
Quantinuum Research LLC, San Diego, California, United States of America,
University of Pennsylvania
University of Copenhagen
Novo Nordisk Foundation
Division of Infection, Immunity and Respiratory Medicine, University of Manchester, Manchester, UK
University of Eastern Finland
Leipzig University
University of Groningen
Population Health Sciences, Bristol, United Kingdom
University of Bristol
University of Oulu
University of Oxford
RIKEN
Vrije Universiteit Amsterdam
Barcelona Institute for Global Health
Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology, Barcelona, Spain
Barcelonaβeta Brain Research Center, Barcelona, Spain
CIBER - Center for Biomedical Research Network
Helmholtz Zentrum München - German Research Center for Environmental Health
School of Medicine and Public Health, Faculty of Medicine and Health, The University of Newcastle, Newcastle, Australia,
University of Turku
Statens Serum Institut
University of Valencia
Jaume I University
University of Gothenburg
Université de Lille
University of Queensland
Area de Salut de Menorca ib-salut, Menorca, Spain,
Fundació Institut d'Investigació Sanitària Illes Balears
Queen Mary University of London
University of Bergen
Norwegian Institute of Public Health
King's College London
Institut national de la santé et de la recherche médicale
University of Cambridge
McMaster University
University of Exeter
Ludwig Maximilian University of Munich
University of the Basque Country
Biocrues-Bizkaia Health Research Institute, Barakaldo, Spain,
Wellcome Sanger Institute
University of Western Australia
Sorbonne Université
Pere Virgili Health Research Institute
Imperial College London
University of Helsinki
National University of Singapore

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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.

Original language	English
Article number	e1008718
Journal	PLoS genetics
Volume	16
Issue number	10
DOIs	https://doi.org/10.1371/journal.pgen.1008718
Publication status	Published - 12 Oct 2020

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@article{ed3319822e7649269c22267646ed004a,

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 = "\{Early Growth Genetics Consortium\} and 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 Marie-Aline Charles and Bo Chawes and Karine Cl{\'e}ment and Ricardo Closa-Monasterolo and Adnan Custovic and Eriksson, \{Johan G.\} and \{van Schaik\}, \{Barbera D. C.\} and Vrijkotte, \{Tanja G. M.\}",

year = "2020",

month = oct,

day = "12",

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

language = "English",

volume = "16",

journal = "PLoS genetics",

issn = "1553-7390",

publisher = "Public Library of Science",

number = "10",

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TY - JOUR

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

AU - Early Growth Genetics Consortium

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 - Closa-Monasterolo, Ricardo

AU - Custovic, Adnan

AU - Eriksson, Johan G.

AU - van Schaik, Barbera D. C.

AU - Vrijkotte, Tanja G. M.

PY - 2020/10/12

Y1 - 2020/10/12

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.

UR - https://www.scopus.com/pages/publications/85092931223

U2 - 10.1371/journal.pgen.1008718

DO - 10.1371/journal.pgen.1008718

M3 - Article

C2 - 33045005

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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