Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits
2 CHOP - Children’s Hospital of Philadelphia
3 Herlev and Gentofte Hospital
4 MAHSC - Manchester Academic Health Science Centre
5 University of Kuopio
6 UCPH - Københavns Universitet = University of Copenhagen = Université de Copenhague
7 Leipzig University / Universität Leipzig
8 UMCG - University Medical Center Groningen [Groningen]
9 University of Bristol [Bristol]
10 University of Oulu [Finland] = Oulun yliopisto [Suomi] = Université d'Oulu [Finlande]
11 The Wellcome Trust Centre for Human Genetics [Oxford]
12 VUB - Vrije Universiteit Brussel [Bruxelles]
13 CIBERESP - Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública = Consortium for Biomedical Research of Epidemiology and Public Health
14 HMGU - Helmholtz Zentrum München = German Research Center for Environmental Health
15 UoN - University of Newcastle [Callaghan, Australia]
16 University of Turku
17 Statens Serum Institut [Copenhagen]
18 Sahlgrenska Academy at University of Gothenburg [Göteborg]
19 EGENODIA (GI3M) - Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283
20 QMUL - Queen Mary University of London
21 NIPH - Norwegian Institute of Public Health [Oslo]
22 King‘s College London
23 University of Groningen [Groningen]
24 UvA - Universiteit van Amsterdam = University of Amsterdam
25 CRESS (U1153 / UMR_A 1125) - Centre for Research in Epidemiology and Statistics | Centre de Recherche Épidémiologie et Statistiques
26 CAM - University of Cambridge [Cambridge, UK]
27 McMaster University [Hamilton, Ontario]
28 University of Exeter
29 LMU - Ludwig Maximilian University [Munich] = Ludwig Maximilians Universität München
30 UPV / EHU - Universidad del País Vasco [Espainia] / Euskal Herriko Unibertsitatea [España] = University of the Basque Country [Spain] = Université du pays basque [Espagne]
31 The Wellcome Trust Sanger Institute [Cambridge]
32 UWA - The University of Western Australia
33 Nutriomics - Nutrition et obésités: approches systémiques (UMR-S 1269)
34 URV - University Rovira i virgili = Universidad Rovira y Virgili = Universitat Rovira i Virgili
35 Imperial College London
36 Helsingin yliopisto = Helsingfors universitet = University of Helsinki
37 VU - Vrije Universiteit Amsterdam [Amsterdam]
38 UCL - University College London [UCL]
39 UiB - University of Bergen
40 University of Tampere [Finland]
41 KUH - Copenhagen University Hospital [Denmark] = Københavns Universitetshospital [Danmark]
42 University of Manchester [Manchester]
43 UQ [All campuses : Brisbane, Dutton Park Gatton, Herston, St Lucia and other locations] - The University of Queensland
44 Haukeland University Hospital
45 UNIMIB - Università degli Studi di Milano-Bicocca = University of Milano-Bicocca
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Résumé
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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