Mediators of the association between childhood body mass index and educational attainment: Analysis of a UK prospective cohort study.

BACKGROUND: Higher body mass index (BMI) in childhood is associated with lower academic achievement. OBJECTIVE: To explore potential pathways linking childhood BMI with educational attainment. METHODS: Using data from the Avon Longitudinal Study of Parents and Children prospective cohort study (N = 6949), we assessed the association between BMI z-scores at 11.7 years and educational attainment at 16 (General Certificate of Secondary Education [GCSE] results). Depressive symptoms, externalizing behaviours, bullying and school enjoyment were considered as potential mediators. Mediators were examined individually and jointly using sequential causal mediation. RESULTS: Higher BMI z-scores were associated with lower GCSE scores (females ß = -3.47 95% CI -5.54, -1.41 males ß = -4.33 95% CI -6.73, -1.94). Together, bullying, externalizing symptoms, depressive symptoms and school enjoyment mediated 41.9% of this association in females, and 23.3% in males. In males, evidence for mediation was weak (confidence intervals for all indirect effects spanned the null). In both females and males, most of the mediation was driven by externalizing symptoms. CONCLUSIONS: The detrimental effect of higher BMI on educational attainment appears to be partly explained by externalizing behaviours, particularly in females. Interventions to support behavioural problems may help the academic achievement of children with a higher body weight.

Molecular mediators of the association between child obesity and mental health.

Biological mechanisms underlying the association between obesity and depression remain unclear. We investigated the role of metabolites and DNA methylation as mediators of the relationship between childhood obesity and subsequent poor mental health in the English Avon Longitudinal Study of Parents and Children. Obesity was defined according to United Kingdom Growth charts at age 7 years and mental health through the Short Mood and Feelings Questionnaire (SMFQ) completed at age 11 years. Metabolites and DNA methylation were measured by nuclear magnetic resonance spectroscopy and Illumina array in blood at the age of 7 years. The associations between obesity and SMFQ score, as continuous count data or using cut-offs to define depressive symptoms (SMFQ >7) or depression (SMFQ >11), were tested using adjusted Poisson and logistic regression. Candidate metabolite mediators were identified through metabolome-wide association scans for obesity and SMFQ score, correcting for false-discovery rate. Candidate DNA methylation mediators were identified through testing the association of putative BMI-associated CpG sites with SMFQ scores, correcting for look-up false-discovery rate. Mediation by candidate molecular markers was tested. Two-sample Mendelian randomization (MR) analyses were additionally applied to test causal associations of metabolites with depression in independent adult samples. 4,018 and 768 children were included for metabolomics and epigenetics analyses, respectively. Obesity at 7 years was associated with a 14% increase in SMFQ score (95% CI: 1.04, 1.25) and greater odds of depression (OR: 1.46 (95% CI: 0.78, 2.38) at 11 years. Natural indirect effects (mediating pathways) between obesity and depression for tyrosine, leucine and conjugated linoleic acid were 1.06 (95% CI: 1.00, 1.13, proportion mediated (PM): 15%), 1.04 (95% CI: 0.99, 1.10, PM: 9.6%) and 1.06 (95% CI: 1.00, 1.12, PM: 13.9%) respectively. In MR analysis, one unit increase in tyrosine was associated with 0.13 higher log odds of depression (p = 0.1). Methylation at cg17128312, located in the FBXW9 gene, had a natural indirect effect of 1.05 (95% CI: 1.01,1.13, PM: 27%) as a mediator of obesity and SMFQ score. Potential biologically plausible mechanisms involving these identified molecular features include neurotransmitter regulation, inflammation, and gut microbiome modulation. These results require replication in further observational and mechanistic studies.