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.
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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DOI：
10.1016/j.drugalcdep.2021.108654
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发表时间：
2021-04-01
影响因子：
4.2
通讯作者：
Zuccolo L
中科院分区：
文献类型：
--
作者：
Easey KE;Wootton RE;Sallis HM;Haan E;Schellhas L;Munafò MR;Timpson NJ;Zuccolo L
一般人群中得出的酒精PRS与怀孕期间的消费有关。孕32周母亲酒精性PRS与围产期抑郁症相关母亲酒精PRS与13岁时子女智力下降相关。后代酒精PRS没有预测后代在青春期的饮酒量。大量饮酒通常与心理健康问题同时发生;这可能是由于混淆，共同的生物机制或因果关系。酒精使用的多基因风险评分（PRS）可用于探索关键生命阶段的这种关联。我们通过以下方式表征了与成人饮酒模式可靠相关的PRS：1）验证它是否预测了在不同生命阶段（怀孕，青春期）自己饮酒对心理健康的影响。此外，我们还探讨了酒精PRS与心理健康表型的关系：2）个体内（使用自己的酒精PRS对自己的表型）和3）代际（使用母亲的酒精PRS对后代表型）。我们使用的数据来自雅芳家长和儿童纵向研究（ALSPAC）（n = 960-7841）。研究了其他物质滥用行为和心理健康/行为结果（酒精表型n = 22;健康表型n = 91）。母亲酒精PRS与妊娠期间的饮酒量相关（最强信号：妊娠18周时的饮酒频率：β = 0.041，95%CI = 0.0.02-0.06），p = 1.01 × 10−5，校正R2 = 1.6%），后代酒精PRS不能预测后代的饮酒量。我们发现母亲酒精PRS与自身围产期抑郁症（OR = 1.10，95%CI = 1.02至1.18，p = 0.022）和后代智力下降（β=-0.209，95%CI-0.38至-0.04，p= 0.016）相关。这些酒精PRS是母亲在怀孕期间饮酒的有效代理。后代酒精PRS与青春期饮酒无关。与不同研究设计的结果一致，我们发现母亲酒精PRS与产前抑郁和后代智力下降有关。
Alcohol PRS derived in the general population associated with consumption during pregnancy. Maternal alcohol PRS associated with perinatal depression at 32 weeks gestation. Maternal alcohol PRS associated with decreased offspring intellectual ability at age 13. Offspring alcohol PRS did not predict offspring alcohol consumption in adolescence. 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. 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). 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). 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.
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通讯作者：
Wells, Nicholas
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