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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.* ; Iñiguez, C.* ; Pitkänen, N.* ; Chesi, A.* ; Bacelis, J.* ; Yengo, L.* ; Torrent, M.* ; Ntalla, I.* ; Helgeland, Ø.* ; Selzam, S.* ; Vonk, J.M.* ; Zafarmand, M.H.* ; Heude, B.* ; Farooqi, I.S.* ; Alyass, A.* ; Beaumont, R.N.* ; Have, C.T.* ; Rzehak, P.* ; Bilbao, J.R.* ; Schnurr, T.M.* ; Barroso, I.* ; Bønnelykke, K.* ; Beilin, L.J.* ; Carstensen, L.* ; Charles, M.A.* ; Chawes, B.* ; Clément, K.* ; Closa-Monasterolo, R.* ; Custovic, A.* ; Eriksson, J.G.* ; Escribano, J.* ; Groen-Blokhuis, M.* ; Grote, V.* ; Gruszfeld, D.* ; Hakonarson, H.* ; Hansen, T.* ; Hattersley, A.T.* ; Hollensted, M.* ; Hottenga, J.J.* ; Hyppönen, E.* ; Johansson, S.* ; Joro, R.* ; Kähönen, M.* ; Karhunen, V.* ; Kiess, W.* ; Knight, B.A.* ; Koletzko, B.* ; Kühnapfel, A.* ; Landgraf, K.* ; Langhendries, J.P.* ; Lehtimäki, T.* ; Leinonen, J.T.* ; Li, A.* ; Lindi, V.* ; Lowry, E.* ; Bustamante, M.* ; Medina-Gomez, C.* ; Melbye, M.* ; Michaelsen, K.F.* ; Morgen, C.S.* ; Mori, T.A.* ; Nielsen, T.R.H.* ; Niinikoski, H.* ; Oldehinkel, A.J.* ; Pahkala, K.* ; Panoutsopoulou, K.* ; Pedersen, O.* ; Pennell, C.E.* ; Power, C.* ; Reijneveld, S.A.* ; Rivadeneira, F.* ; Simpson, A.* ; Sly, P.D.* ; Stokholm, J.* ; Teo, K.K.* ; Thiering, E. ; Timpson, N.J.* ; Uitterlinden, A.G.* ; Zeggini, E. ; van Beijsterveldt, C.E.M.* ; van Schaik, B.D.C.* ; Vaudel, M.* ; Verduci, E.*

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

PLoS Genet. 16:e1008718 (2020)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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 nearNEDD4LandSLC45A3, 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.Author summary Although twin studies have shown that body mass index (BMI) is highly heritable, many common genetic variants involved in the development of BMI have not yet been identified, especially in children. We studied associations of more than 40 million genetic variants with childhood BMI in 61,111 children aged between 2 and 10 years. We identified 25 genetic variants that were associated with childhood BMI. Two of these have not been implicated for BMI previously, located close to the genesNEDD4LandSLC45A3. We also show that the genetic background of childhood BMI overlaps with that of birth weight, adult BMI, waist-to-hip-ratio, diastolic blood pressure, type 2 diabetes, and age at menarche. Our results suggest that the biological processes underlying childhood BMI largely overlap with those underlying adult BMI. However, the overlap is not complete. Additionally, the genetic backgrounds of childhood BMI and other cardio-metabolic phenotypes are overlapping. This may mean that the associations of childhood BMI and later cardio-metabolic outcomes are partially explained by shared genetics, but it could also be explained by the strong association of childhood BMI with adult BMI.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Prostate-specific Antigen; Genome-wide Association; Mendelian Randomization; Cardiovascular Risk; Genetic-variation; Pooled Analysis; Young-adults; Obesity; Overweight; Adiposity
ISSN (print) / ISBN 1553-7390
e-ISSN 1553-7404
Journal PLoS Genetics
Quellenangaben Volume: 16, Issue: 10, Pages: , Article Number: e1008718 Supplement: ,
Publisher Public Library of Science (PLoS)
Publishing Place 1160 Battery Street, Ste 100, San Francisco, Ca 94111 Usa
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology (EPI)
Institute of Epidemiology II (EPI2)
Institute of Translational Genomics (ITG)
Grants National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust
American Diabetes Association
Daniel B. Burke Chair for Diabetes Research
NIH
Agencia de Gestio d'Ajuts Universitaris i de Recerca
Generalitat de Catalunya -Fons Social Europeu
European Research Council Advanced Grant META-GROWTH (ERC-2012-AdG)
Oak Foundation Fellowship
ZonMw
NIHR
University College London
Wellcome
NIDDK
Wellcome Trust
Royal Society
Wellcome Trust Senior Investigator award
NIHR Cambridge Biomedical Research Centre
Botnar Foundation
Bernard Wolfe Health Neuroscience Endowment
European Community's Seventh Framework Programme (FP7/2007-2013) project Beta-JUDO
University of Bristol
UK Medical Research Council
Medical Research Council
European Research Council
Canada Research Chair
Finnish Cultural Foundation
KNAW Academy Professor Award
TARGET
Danish Diabetes Academy
Copenhagen Graduate School of Health and Medical Sciences
Netherlands Organization for Health Research and Development (VIDI)
European Research Council (ERC)
French National Agency of Research, F-CRIN/FORCE