Disentangling differing relationships between internalizing disorders and alcohol use

IF 1.6 3区 医学 Q3 GENETICS & HEREDITY American Journal of Medical Genetics Part B: Neuropsychiatric Genetics Pub Date : 2024-02-20 DOI:10.1002/ajmg.b.32975
Maizy S. Brasher, Andrew D. Grotzinger, Naomi P. Friedman, Harry R. Smolker, Luke M. Evans
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Abstract

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.

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消除内化障碍与酗酒之间的不同关系。
内化障碍和酗酒都会对全球健康产生巨大而广泛的影响。先前的研究已经确定了这些疾病的共同表型合并症,以及它们的共同遗传变异。我们利用基因组结构方程模型研究了内化、外化和饮酒特征的共同遗传学,并探讨了内化症状的特定领域是否介导了与饮酒相比与问题性饮酒的对比关系。我们还研究了其他芬兰和东亚血统群体中类似特征之间的遗传相关模式。当考虑到外化性精神病理学的共同遗传影响时,内化性特征对酒精使用的遗传效应有所降低,这表明多种精神障碍的共同遗传因素及其对内化性特征和酒精使用特征合并症的遗传影响发挥着重要作用。个体内化特征对饮酒频率的影响截然不同,这表明即使在相似的疾病中也存在复杂的多效性系统,而如果只评估正式诊断之间的关系,则可能会忽略这些多效性系统。未来的研究工作必须考虑到共同心理病理学的广泛影响以及障碍内部异质性的细微影响,从而更全面地了解复杂特质的生物学基础。
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来源期刊
CiteScore
5.90
自引率
7.10%
发文量
40
审稿时长
4-8 weeks
期刊介绍: Neuropsychiatric Genetics, Part B of the American Journal of Medical Genetics (AJMG) , provides a forum for experimental and clinical investigations of the genetic mechanisms underlying neurologic and psychiatric disorders. It is a resource for novel genetics studies of the heritable nature of psychiatric and other nervous system disorders, characterized at the molecular, cellular or behavior levels. Neuropsychiatric Genetics publishes eight times per year.
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