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

Laura Schellhas,Hannah M Sallis,Robyn E Wootton,Elis Haan,Luisa Zuccolo,Marcus R Munafò,Kayleigh E Easey,Gemma C Sharp

doi:10.1111/add.15521

Laura Schellhas, Hannah M Sallis + Show 6 more

Open Access

https://doi.org/10.1111/add.15521

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Abstract

Background and aimsPrevious 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.DesignSecondary 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.SettingWe used data from a longitudinal birth cohort study from England, the Avon Longitudinal Study of Parents and Children (ALSPAC).ParticipantsOur sample included 7921 mothers and 7964 offspring.MeasurementsMental 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).FindingsThe maternal smoking and caffeine GRS were associated with maternal smoking and caffeine consumption during pregnancy (2nd trimester: Psmoking = 3.0 × 10−7, Pcaffeine = 3.28 × 10−5). Both the maternal and offspring smoking GRS showed evidence of association with reduced childhood anxiety symptoms (βmaternal = −0.033; βoffspring = −0.031) and increased conduct disorder symptoms (βmaternal = 0.024; βoffspring = 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.ConclusionsWe 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.

Highlights

Smoking and caffeine consumption often co-occur [1] and are associated with mental health problems and other substance use behaviours [2,3]
Associations between smoking, caffeine and mental health outcomes within individuals, observational research suggests that prenatal maternal consumption of tobacco and caffeine could have an intergenerational effect on offspring’s mental health [7,8,9,10]
Our results showed that the maternal smoking and caffeine genetic risk scores (GRS) are valid predictors of smoking and caffeine consumption from tea and coffee during pregnancy

Summary

Introduction

Smoking and caffeine consumption often co-occur [1] and are associated with mental health problems and other substance use behaviours [2,3]. Do mothers and offspring share a similar environment (such as socioeconomic position), they share, on average, 50% of their segregating genetic variation Because of this shared genetic and environmental confounding, it is difficult to disentangle the effect of maternal substance use on offspring mental health from those of offspring’s own substance use. Previous studies suggest an association between maternal tobacco and caffeine consumption during and outside of pregnancy and offspring mental health. 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. The caffeine GRS showed weaker evidence for associations with mental health outcomes

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