The association of alcohol polygenic risk scores with mental health outcomes: A multi-generational analysis in the Avon Longitudinal Study of Parents and Children

Background: Increased alcohol consumption often co-occurs with mental health problems; however, we do not currently fully understand whether this is due to confounding, shared biological mechanisms, or causal effects. Design: We analysed a polygenic risk score (PRS) composed of single nucleotide polymorphisms (SNPs) reliably associated with patterns of adult alcohol consumption to test: 1) if this PRS is associated with consumption during pregnancy and adolescence, 2) if child alcohol PRS is associated with mental health phenotypes, and 3) if maternal alcohol PRS is associated with offspring alcohol phenotypes and mental health. We used data from the Avon Longitudinal Study of Parents and Children (ALSPAC). Additional substance abuse behaviours and mental health/behavioural outcomes were also investigated at different life stages across both generations (alcohol phenotypes n =22; health phenotypes n = 91). The availability of data from early life on the same participants (pre-alcohol use around ages 7-10 years) provided a negative control, in contrast to that in ages of alcohol use (13-24 years). Findings: The adult alcohol PRS was associated with consumption phenotypes during pregnancy (strongest signal for alcohol frequency at 18 weeks gestation: p=1.01x10-5) but offspring alcohol PRS did not predict offspring alcohol consumption at age 13-24 years. We found evidence for an association of maternal PRS with own perinatal depression (p=0.02) and decreased offspring intellectual ability (p=0.016). Conclusions: An alcohol PRS derived from GWAS of alcohol use in the general population was shown to be associated with frequency and amount of alcohol consumed during pregnancy, and maternal depression at 32 weeks gestation. The associations between alcohol PRS with mothers depression and offspring intellectual ability are consistent with previous studies, adding to the validity of using this alcohol PRS in future aetiological studies.