Both internalizing disorders and alcohol use have dramatic, wide‐spread implications for global health. Previous work has established common phenotypic comorbidity among these disorders, as well as shared genetic variation underlying them both. We used genomic structural equation modeling to investigate the shared genetics of internalizing, externalizing, and alcohol use traits, as well as to explore whether specific domains of internalizing symptoms mediate the contrasting relationships with problematic alcohol use compared to alcohol consumption. We also examined patterns of genetic correlations between similar traits within additional Finnish and East Asian ancestry groups. When the shared genetic influence of externalizing psychopathology was accounted for, the genetic effect of internalizing traits on alcohol use was reduced, suggesting the important role of common genetic factors underlying multiple psychiatric disorders and their genetic influences on comorbidity of internalizing and alcohol use traits. Individual internalizing domains had contrasting effects on frequency of alcohol consumption, which demonstrate the complex system of pleiotropy that exists, even within similar disorders, and can be missed when evaluating only relationships among formal diagnoses. Future work must consider the broad effects of shared psychopathology along with the fine‐scale effects of heterogeneity within disorders to more fully understand the biology underlying complex traits.

中文翻译：

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理清内化障碍与饮酒之间的不同关系

内化障碍和饮酒都会对全球健康产生巨大而广泛的影响。先前的工作已经确定了这些疾病之间常见的表型合并症，以及它们背后的共同遗传变异。我们使用基因组结构方程模型来研究内化、外化和饮酒特征的共同遗传学，并探讨内化症状的特定领域是否介导与有问题的饮酒与饮酒相比的对比关系。我们还研究了其他芬兰和东亚血统群体中相似特征之间的遗传相关性模式。当考虑到外化精神病理学的共同遗传影响时，内化特征对饮酒的遗传影响就会降低，这表明多种精神疾病的共同遗传因素及其遗传对内化特征和酒精使用特征共病的影响具有重要作用。个体内化域对饮酒频率具有截然不同的影响，这表明即使在类似的疾病中也存在复杂的多效性系统，并且在仅评估正式诊断之间的关系时可能会被忽略。未来的工作必须考虑共同的精神病理学的广泛影响以及疾病内异质性的精细尺度影响，以更全面地理解复杂特征背后的生物学。