Characterization of alcohol polygenic risk scores in the context of mental health outcomes: Within-individual and intergenerational analyses in the Avon Longitudinal Study of Parents and Children

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Abstract

Background
Heavy alcohol consumption often co-occurs with mental health problems; this could be due to confounding, shared biological mechanisms, or causal effects. Polygenic risk scores (PRS) for alcohol use can be used to explore this association at critical life stages.

Design
We characterized a PRS reliably associated with patterns of adult alcohol consumption by 1) validating whether it predicts own alcohol use at different life-stages (pregnancy, adolescence) of interest for mental health impact. Additionally, we explored associations of alcohol PRS on mental health phenotypes 2) within-individuals (using own alcohol PRS on own phenotypes) and 3) intergenerationally (using maternal alcohol PRS on offspring phenotypes). We used data from the Avon Longitudinal Study of Parents and Children (ALSPAC) (n = 960–7841). Additional substance abuse behaviors and mental health/behavioral outcomes were investigated (alcohol phenotypes n = 22; health phenotypes n = 91).

Findings
Maternal alcohol PRS was associated with consumption during pregnancy (strongest signal: alcohol frequency at 18 weeks’ gestation: β = 0.041, 95%CI = 0.0.02–0.06), p = 1.01 × 10−5, adjusted R2 = 1.6 %), offspring alcohol PRS did not predict offspring alcohol consumption. We found evidence for an association of maternal alcohol PRS with own perinatal depression (OR  = 1.10, 95% CI = 1.02 to 1.18, p = 0.022) and decreased offspring intellectual ability (β=-0.209, 95% CI -0.38 to -0.04, p= 0.016).

Conclusions
These alcohol PRS are a valid proxy for maternal alcohol use in pregnancy. Offspring alcohol PRS was not associated with drinking in adolescence. Consistently with results from different study designs, we found evidence that maternal alcohol PRS are associated with both prenatal depression and decreased offspring intellectual ability.
Original languageEnglish
Article number108654
Number of pages8
JournalDrug and Alcohol Dependence
Volume221
Early online date27 Feb 2021
DOIs
Publication statusPublished - 1 Apr 2021

Bibliographical note

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. This work was supported by the UK Medical Research Council and the Wellcome Trust (Grant ref: 102215/2/13/2) and the University of Bristol provide which provide core support for ALSPAC. This work was performed in the UK Medical Research Council Integrative Epidemiology Unit, jointly funded by the University of Bristol and the UK MRC , in which MRM leads one of the programmes ( MC_UU_00011/7) . The MRC also funded KEE’s PhD studentship. LZ was supported by a UK Medical Research Council fellowship (grant number G0902144 ). This research was also supported by the NIHR Bristol Biomedical Research Centre at 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 National Institute for Health Research or the Department of Health and Social Care. NJT is a Wellcome Trust Investigator (202802/Z/16/Z), is the PI of the Avon Longitudinal Study of Parents and Children (MRC and WT 102215/2/13/2), is supported by the University of Bristol NIHR Biomedical Research Centre ( BRC-1215-20011 ), the MRC Integrative Epidemiology Unit and works within the CRUK Integrative Cancer Epidemiology Programme ( C18281/A19169 ). LS and EH are funded by CAPICE (Childhood and Adolescence Psychopathology: unravelling the complex etiology by a large Interdisciplinary Collaboration in Europe) 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. The UK Medical Research Council also funded the most recent collection of alcohol information in the ALSPAC participants (grant number MR/L033306/1. A comprehensive list of grants funding is available on the ALSPAC website ( http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf ).

Publisher Copyright:
© 2021 The Author(s)

Keywords

  • Alcohol
  • Mental health
  • Polygenic risk score
  • MR-PheWAS
  • ALSPAC

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