ObjectivesTo assess the causal relationship of different health conditions in childhood and adolescence with educational attainment and school absence. DesignLongitudinal observational study and Mendelian randomization (MR) analyses. SettingAvon Longitudinal Study of Parents and Children (ALSPAC), a population sample of children from South-West England born in 1991-1992. Participants6113 unrelated children with available GCSE records and genetic data (50% female). ExposuresSix common health conditions with known genetic markers measured at age 10 (primary school) and 13 (mid-secondary school). These were: symptoms of Attention-Deficit Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), depression, asthma, migraines and BMI. Genetic liability for these conditions and BMI was indexed by polygenic scores. Main outcome measuresEducational attainment at age 16 (total GCSE and equivalents points score), school absence at age 14-16. ResultsIn multivariate-adjusted observational models, all health conditions except asthma and migraines were associated with poorer educational attainment and greater school absence. Substantial mediation by school absence was seen for BMI (e.g. 35.6% for BMI at 13) and migraines (67% at age 10), with more modest mediation for behavioural and neurodevelopmental measures of health. In genetic models, a unit increase in genetically instrumented BMI z-score at age 10 predicted a 0.19 S.D. decrease (95% CI: -0.28 to -0.11) in attainment at 16, equivalent to around a 1/3 grade difference in each subject. It also predicted 8.6% more school absence (95% CI:1.3%, 16.5%). Similar associations were seen for BMI at age 13. Consistent with previous work, genetic liability for ADHD predicted lower educational attainment, but did not clearly increase school absence. ConclusionsTriangulation across multiple approaches supported a causal, negative influence of higher BMI on educational attainment and school absence. Further research is required to understand the mechanisms linking higher BMI with school absence and attainment. What is already known on this topicO_LIOn average, children with common health conditions have worse educational attainment C_LIO_LIIt is unclear whether all health-attainment and health-absenteeism associations are causal, or reflect confounding by social and economic circumstances C_LIO_LIWe do not know how much health-related school absenteeism contributes to these associations C_LI What this study addsO_LIResults support a negative influence of high BMI in secondary school on educational attainment (GCSEs) and absenteeism C_LIO_LIAbsenteeism substantially mediated BMI-GCSE associations, suggesting a target for intervention C_LIO_LIThere was less evidence for causal effects of Autism Spectrum Disorder, depressive symptoms, asthma or migraines on attainment and absenteeism C_LIO_LIContribution of absenteeism to ADHD-GCSE associations was modest, suggesting interventions should target other mechanisms C_LI

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