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

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

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Abstract

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 1) validated smoking and caffeine genetic risk scores (GRS) derived from published GWAS for use during pregnancy, 2) compared estimated effects of maternal and offspring GRS on childhood mental health outcomes, and 3) 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: Psmoking = 3.0x10-7 , Pcaffeine = 3.28x10-5 ). 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.

CONCLUSIONS: We did not find strong evidence that maternal smoking and caffeine genetic risk scores (GRS) have a causal effect on offspring mental health outcomes. Our results confirm that the smoking GRS also captures liability for sensation seeking personality traits.

Original languageEnglish
Pages (from-to)3153-3166
Number of pages14
JournalAddiction
Volume116
Issue number11
Early online date10 May 2021
DOIs
Publication statusE-pub ahead of print - 10 May 2021

Bibliographical note

Funding Information:
This research was performed in the UK Medical Research Council Integrative Epidemiology Unit (grant number: MC_UU_00011/7) and also supported by the National Institute for Health Research (NIHR) Bristol Biomedical Research Centre at University Hospitals Bristol National Health Service (NHS) Foundation Trust and the University of Bristol. The Medical Research Council (MRC) also funded K.E.E.'s PhD studentship. L.Z. was supported by a UK MRC fellowship (grant number G0902144). G.C.S. was supported by the MRC (New Investigator Research Grant, MR/S009310/1) and the European Joint Programming Initiative ‘A Healthy Diet for a Healthy Life’ (JPI HDHL, NutriPROGRAM project, UK MRC MR/S036520/1).

Funding Information:
We are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses. The UK Medical Research Council and Wellcome (Grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors and L.S. and E.H. will serve as guarantors for the contents of this paper.

Funding Information:
This research was also conducted as part of the Childhood and Adolescence Psychopathology: unravelling the complex aetiology by a large Interdisciplinary Collaboration in Europe (CAPICE) project, funded by the European Union's Horizon 2020 research and innovation programme, Marie Sklodowska Curie Actions–MSCA‐ITN‐2016–Innovative Training Networks under grant agreement number 721567. This study was supported by the NIHR Biomedical Research Centre at the University Hospitals Bristol NHS Foundation Trust and the University of Bristol. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.

Funding Information:
This research was performed in the UK Medical Research Council Integrative Epidemiology Unit (grant number: MC_UU_00011/7) and also supported by the National Institute for Health Research (NIHR) Bristol Biomedical Research Centre at University Hospitals Bristol National Health Service (NHS) Foundation Trust and the University of Bristol. The Medical Research Council (MRC) also funded K.E.E.'s PhD studentship. L.Z. was supported by a UK MRC fellowship (grant number G0902144). G.C.S. was supported by the MRC (New Investigator Research Grant, MR/S009310/1) and the European Joint Programming Initiative ?A Healthy Diet for a Healthy Life? (JPI HDHL, NutriPROGRAM project, UK MRC MR/S036520/1). This research was also conducted as part of the Childhood and Adolescence Psychopathology: unravelling the complex aetiology by a large Interdisciplinary Collaboration in Europe (CAPICE) project, funded by the European Union's Horizon 2020 research and innovation programme, Marie Sklodowska Curie Actions?MSCA-ITN-2016?Innovative Training Networks under grant agreement number 721567. This study was supported by the NIHR Biomedical Research Centre at the University Hospitals Bristol NHS Foundation Trust and the University of Bristol. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. A comprehensive list of grant funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf). GWAS data was generated by Sample Logistics and Genotyping Facilities at Wellcome Sanger Institute and LabCorp (Laboratory Corporation of America) using support from 23andMe. We are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses. The UK Medical Research Council and Wellcome (Grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors and L.S. and E.H. will serve as guarantors for the contents of this paper.

Publisher Copyright:
© 2021 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.

Keywords

  • ALSPAC
  • caffeine
  • genetic risk score
  • intergenerational effects
  • mental health
  • tobacco

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