Sanofi Aventis, Servier & Takeda. MS receives funding from Pfizer Inc. for a project not related to this research. IB and spouse own stock in GlaxoSmithKline and Incyte Corp. ZE and CDB currently serve on the editorial board of PLOS Genetics. AC reports personal fees from Novartis, personal fees from Thermo Fisher Scientific, personal fees from Philips, personal fees from Sanofi, personal fees from Stallergenes Greer, outside the submitted work. KC in involved in consultancy for Danone Research, LNC-therapeutic and Confo-therapeutic but no personal funding is received and this activity not linked to the present research.

Background DNA methylation has been shown to be associated with adiposity in adulthood. However, whether similar DNA methylation patterns are associated with childhood and adolescent body mass index (BMI) is largely unknown. More insight into this relationship at younger ages may have implications for future prevention of obesity and its related traits. Methods We examined whether DNA methylation in cord blood and whole blood in childhood and adolescence was associated with BMI in the age range from 2 to 18 years using both cross-sectional and longitudinal models. We performed meta-analyses of epigenome-wide association studies including up to 4133 children from 23 studies. We examined the overlap of findings reported in previous studies in children and adults with those in our analyses and calculated enrichment. Results DNA methylation at three CpGs (cg05937453, cg25212453, and cg10040131), each in a different age range, was associated with BMI at Bonferroni significance, P < 1.06 × 10−7, with a 0.96 standard deviation score (SDS) (standard error (SE) 0.17), 0.32 SDS (SE 0.06), and 0.32 BMI SDS (SE 0.06) higher BMI per 10% increase in methylation, respectively. DNA methylation at nine additional CpGs in the cross-sectional childhood model was associated with BMI at false discovery rate significance. The strength of the associations of DNA methylation at the 187 CpGs previously identified to be associated with adult BMI, increased with advancing age across childhood and adolescence in our analyses. In addition, correlation coefficients between effect estimates for those CpGs in adults and in children and adolescents also increased. Among the top findings for each age range, we observed increasing enrichment for the CpGs that were previously identified in adults (birth Penrichment = 1; childhood Penrichment = 2.00 × 10−4; adolescence Penrichment = 2.10 × 10−7). Conclusions There were only minimal associations of DNA methylation with childhood and adolescent BMI. With the advancing age of the participants across childhood and adolescence, we observed increasing overlap with altered DNA methylation loci reported in association with adult BMI. These findings may be compatible with the hypothesis that DNA methylation differences are mostly a consequence rather than a cause of obesity.

Background/ObjectivesThe aim of this study was to examine the effect of physical activity (PA) and sedentary behaviour (SB) on body mass index (BMI) and fat mass index (FMI) in children over the course of five years and identify potential bi-directional associations.Subjects/MethodsData were drawn from the EU Childhood Obesity Project (CHOP). PA and SB were measured with the SenseWear Armband 2 at the ages of 6 (T1), 8 (T2) and 11 (T3) years. Height and weight were measured and BMI was calculated at each time point, resulting in 1254 complete observations from 600 children. Bio impedance analysis was used to measure body fat mass and eventually calculate FMI. To examine the longitudinal association between PA/SB and BMI/FMI as well as to account for repeated measure on these children, mixed model analysis was employed.ResultsHigher levels of total PA and moderate-to-vigorous PA (MVPA) were associated with lower BMI and FMI and higher SB with higher BMI and FMI over the five year period. When looking at the age dependent effects, negative associations of MVPA (βMVPA x age: − 0.05, 95% confidence interval (CI): − 0.09 – -0.01, p = 0.007) and positive associations of SB (βSB x age: 0.04, 95% CI: 0.02–0.06, p < 0.001) increased with each year of age. In a model combining these two effects, only SB x age interaction remained significant (βSB x age: 0.04, 95% CI: 0.03–0.06, p = 0.01). No significant interaction between MVPA and SB could be discerned. Light Physical activity showed no significant associations with BMI or FMI. When reversing outcome and predictor; higher BMI or FMI showed a negative association with MVPA and a positive association with SB, but no age dependency.ConclusionsMore time per day in SB was associated with a higher BMI over the course of five years, whereas higher MVPA had an inverse effect. In a combined model, only effects of higher SB remained significant, emphasizing the importance of SB in obesity prevention. Present bidirectional associations, where lower body size was associated with higher PA and lower SB, indicated the need for an integrated approach of activity and weight control for obesity prevention.Trial registrationClinicalTrials.gov Identifier: NCT00338689. Registered: June 19, 2006 (retrospectively registered).Electronic supplementary materialThe online version of this article (10.1186/s12966-018-0756-3) contains supplementary material, which is available to authorized users.

Physical activity (PA) is presumed to decline during childhood and adolescence, but only few long-term studies about PA development during this period of life exist. We assessed PA and sedentary behavior (SB) over a 5-year period to gain a better understanding of the extent of change in activity and potential influencing factors. METHODS: PA and SB of 600 children from the Childhood Obesity Project were objectively measured with the SenseWear Armband 2 at the ages of 6, 8, and 11 years, resulting in 1254 observations. Longitudinal changes of total PA, moderate-to-vigorous physical activity (MVPA), light physical activity (LPA), and SB were modeled with mixed-effects models. RESULTS: Total PA revealed a significant quadratic decline with age (P < .001), resulting in a change of total PA by −75.3 minutes per day from 6 to 11 years. LPA linearly declined (P < .001) by 44.6 minutes per day, MVPA quadratically declined (P < .001) by an overall 30.7 minutes, whereas SB increased significantly (+107 minutes; P = .001). Boys showed a steeper decline in LPA (P = .003) and MVPA (P < .001) than did girls. Higher fat mass index and BMI z scores were associated with lower levels of total PA and MVPA and higher levels of SB (all P < .001). CONCLUSIONS: We showed that PA decreased, and SB increased in earlier years than previously thought. MVPA remained relatively stable until 8 years, but revealed a drop-off at 11 years, identifying this period as a crucial time for intervention.

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