Objective: Molecular genetic studies of alcohol and nicotine have identified many genome-wide loci. We examined the predictive utility of drinking and smoking polygenic scores (PGS) for alcohol and nicotine use from late childhood to early adulthood, substance-specific versus broader-liability PGS effects, and if PGS performance varied between consumption versus pathological use. Methods: Latent growth curve models with structured residuals were used to assess the predictive utility of drinks per week and regular smoking PGS for measures of alcohol and nicotine consumption and problematic use from age 14 to 34. PGSs were generated from the largest discovery sample for alcohol and nicotine use to date (i.e., GSCAN), and examined for associations with alcohol and nicotine use in the Minnesota Twin Family Study (N=3225). Results: The drinking PGS was a significant predictor of age 14 problematic alcohol use and increases in problematic use during young adulthood. The smoking PGS was a significant predictor for all nicotine use outcomes. After adjusting for the effects of both PGSs, the smoking PGS demonstrated incremental predictive utility for most alcohol use outcomes and remained a significant predictor of nicotine use trajectories. Conclusions: Higher PGS for drinking and smoking were associated with more problematic levels of substance use longitudinally. The smoking PGS seems to capture both nicotine-specific and non-specific genetic liability for substance use, and may index genetic risk for broader externalizing behavior. Validation of PGS within longitudinal designs may have important clinical implications should future studies support the clinical utility of PGS for substance use disorders.

中文翻译：

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多基因评分可预测从青春期到成年期的酒精和尼古丁使用问题的发展

目的：酒精和尼古丁的分子遗传学研究已经确定了许多全基因组位点。我们研究了饮酒和吸烟多基因评分（PGS）在儿童期末至成年初期对酒精和尼古丁使用的预测效用，物质特异性与更广泛的PGS效应之间的关系，以及在消费与病理使用之间PGS的表现是否存在差异。方法：使用具有结构残差的潜伏增长曲线模型来评估每周饮酒和常规吸烟PGS的预测效用，以测量14至34岁之间的酒精和尼古丁消耗量及使用困难。和迄今为止的尼古丁使用情况（即GSCAN），并在明尼苏达州双胞胎家庭研究（N = 3225）中检查了与酒精和尼古丁使用的关联。结果：饮用PGS是14岁以下成年酒精使用困难和成年后使用困难增加的重要预测指标。吸烟PGS是所有尼古丁使用结果的重要预测指标。调整了两种PGS的作用后，吸烟PGS对大多数酒精使用结果均显示出递增的预测效用，并且仍是尼古丁使用轨迹的重要预测指标。结论：吸烟和吸烟的PGS较高，与纵向使用物质的问题量更多有关。吸烟的PGS似乎捕获了尼古丁对物质使用的特异性和非特异性遗传责任，并且可能为更广泛的外在行为指示了遗传风险。