Maternal and child genetic liability for smoking and caffeine consumption and child mental health: an intergenerational genetic risk score analysis in the ALSPAC cohort

Background and aims Previous studies suggest an association between maternal tobacco and caffeine consumption during and outside of pregnancy and offspring mental health. We aimed to separate effects of the maternal environment (intrauterine or postnatal) from pleiotropic genetic effects. Design Secondary analysis of a longitudinal study. We (i) validated smoking and caffeine genetic risk scores (GRS) derived from published genome-wide association study (GWAS) for use during pregnancy, (ii) compared estimated effects of maternal and offspring GRS on childhood mental health outcomes and (iii) tested associations between maternal and offspring GRS on their respective outcomes. Setting We used data from a longitudinal birth cohort study from England, the Avon Longitudinal Study of Parents and Children (ALSPAC). Participants Our sample included 7921 mothers and 7964 offspring. Measurements Mental health and non-mental health phenotypes were derived from questionnaires and clinical assessments: 79 maternal phenotypes assessed during and outside of pregnancy and 71 offspring phenotypes assessed in childhood (<10 years) and adolescence (11-18 years). Findings The maternal smoking and caffeine GRS were associated with maternal smoking and caffeine consumption during pregnancy (2nd trimester: P-smoking = 3.0 x 10(-7), P-caffeine = 3.28 x 10(-5)). Both the maternal and offspring smoking GRS showed evidence of association with reduced childhood anxiety symptoms (beta(maternal) = -0.033; beta(offspring) = -0.031) and increased conduct disorder symptoms (beta(maternal) = 0.024; beta(offspring) = 0.030), after correcting for multiple testing. Finally, the maternal and offspring smoking GRS were associated with phenotypes related to sensation seeking behaviours in mothers and adolescence (e.g. increased symptoms of externalising disorders, extraversion and monotony avoidance). The caffeine GRS showed weaker evidence for associations with mental health outcomes. Conclusions We did not find strong evidence that maternal smoking and caffeine genetic risk scores have a causal effect on offspring mental health outcomes. Our results confirm that the smoking genetic risk scores also captures liability for sensation seeking personality traits.