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.
FörderungenNational 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