Abstract
BackgroundHeavy 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. DesignWe 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). FindingsMaternal 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). ConclusionsThese 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.
Highlights
Alcohol use frequently co-occurs with mental health problems (Jane-Llopis and Matytsina, 2006; Mamluk et al, 2020; Skogen et al, 2014), but we do not yet fully understand the nature and extent of these associations
In the second stage of our analysis, we used these polygenic risk scores (PRS) for alcohol con sumption to investigate the association between alcohol consumption and mental health. We did this in two ways: first, we explored if maternal and offspring own alcohol PRS were associated with own mental health using a targeted Mendelian random isation phenome-wide association study (MR-PheWAS) design
We have shown that PRS for alcohol consumption reliably associates with consumption in pregnancy, but not in adolescence/young adult hood
Summary
Alcohol use frequently co-occurs with mental health problems (Jane-Llopis and Matytsina, 2006; Mamluk et al, 2020; Skogen et al, 2014), but we do not yet fully understand the nature and extent of these associations. One way to explore the association between alcohol use and mental health outcomes, is using polygenic risk scores (PRS). 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. 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). With results from different study designs, we found evidence that maternal alcohol PRS are associated with both prenatal depression and decreased offspring in tellectual ability
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