Using genetically informed designs to understand the impact of parental divorce/separation and parental marital discord on offspring alcohol outcomes

项目摘要 这项建议的目的是促进对父母通过哪些机制 离婚/分居和婚姻不和对子女酒精使用障碍(AUD)及相关结局的影响 (例如，初次饮酒和酗酒的年龄较早)。人们普遍认为父母离婚/分居和 父母的婚姻不和对子女的饮酒结果有直接的致病作用。然而，有一个有限的 对遗传因素在这些关联中的作用的认识，尽管有提示证据表明，后代 暴露在父母婚姻问题中也会遗传AUD遗传倾向，而且AUD基因 倾向可以使个人对环境应激源的不利影响敏感。这强调了 有必要研究遗传因素和这些常见的家庭逆境的汇合，以了解它们的 关于后代饮酒结果的共同遗产。这里的目标是使用来自两个国家的数据来解决这个差距 代际、遗传信息研究。第一项是弗吉尼亚成人双胞胎精神病学和 物质使用障碍，从出生就招募的欧洲血统双胞胎样本(N=9345，45%女性) 收集了所有双胞胎加上一部分父母的直接精神访谈数据的记录 (n=1472人，58%为女性)，并通过诊断精神病家族史收集额外的父母数据 对这对双胞胎的采访。第二个是酒精中毒遗传学的合作研究(N=11561，53% 女性)，一项对不同种族(69%的欧洲裔美国人，31%的非裔美国人)的分子遗传学研究 主要通过寻求治疗的先证者招募的家庭样本，其精神病访谈数据 从所有参与者那里收集。这两个样本相互提供信息，以允许检查 研究结果在不同方法和人群中的概括性和趋同性。在生物的指引下- 生态框架，目的是：(1)检查父母之间的关联程度 离婚/分居、父母婚姻不和和子女饮酒结果反映了直接的(即“因果”)影响 和共同的遗传效应；以及(2)检查后代的遗传因素是否预测他们的 对父母离婚/分居和父母婚姻不和的反应。这一结果可能具有理论上的 对酒精问题的遗传风险的间接环境途径的影响 在家庭中传播(即基因与环境的相关性)，以及对基因如何 影响赋予对家庭应激源(即，基因-环境交互作用)的敏感性。反过来，结果可能会 告知临床医生预防家庭子女酗酒的心理教育工作 经历婚姻痛苦和离婚。更广泛地说，这项工作将有助于实现 早期研究人员Pi的研究计划描绘了遗传因素与密切关系 各种因素共同影响酒精滥用的开始、持续和中断。

Project Summary The objective in this proposal is to advance the understanding of the mechanisms through which parental divorce/separation and marital discord influence offspring alcohol use disorder (AUD) and related outcomes (e.g., earlier age at first drink and alcohol misuse). It is commonly thought that parental divorce/separation and parental marital discord have direct, pathogenic effects on offspring alcohol outcomes. Yet, there is a limited appreciation of the role of genetic factors in these associations, despite suggestive evidence that offspring exposed to parental marital problems also inherit AUD genetic predispositions, and that AUD genetic predispositions can sensitize individuals to the adverse effects of environmental stressors. This underscores the need to study the confluence of genetic factors and these common family adversities to understand their joint legacy on offspring alcohol outcomes. The goal here is to address this gap using data from two intergenerational, genetically-informative studies. The first is the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders, a sample of European ancestry twins (N=9345, 45% female) recruited from birth records for whom direct psychiatric interview data were collected on all twins plus a subset of parents (N=1472, 58% female), with additional parental data collected via diagnostic psychiatric family history interviews with the twins. The second is the Collaborative Study on the Genetics of Alcoholism (N=11561, 53% female), a molecular genetic study of an ethnically diverse (69% European American, 31% African American) sample of families primarily recruited via treatment-seeking probands for whom psychiatric interview data were collected from all participants. These two samples are mutually informative in permitting examination of the generalizability and convergence of findings across different methods and populations. Guided by a bio- ecological framework, the aims are to: (1) examine the extent to which associations between parental divorce/separation, parental marital discord, and offspring alcohol outcomes reflect direct (i.e., ‘causal’) effects versus shared genetic effects; and (2) examine whether offspring genetic factors predict variability in their responses to parental divorce/separation and parental marital discord. The results may have theoretical implications for the indirect, environmental pathways through which genetic risk for alcohol problems is transmitted in families (i.e., gene-environment correlation), as well as an understanding of how genetic influences confer sensitivity to familial stressors (i.e., gene-environment interaction). In turn, the results may inform clinicians’ psychoeducation efforts to prevent alcohol misuse among offspring from families experiencing marital distress and divorce. More broadly, this work will contribute to the long-term goal of the Early Stage Investigator PI’s program of research to delineate how genetic factors and close relationship factors come together to influence the onset, persistence, and discontinuity of alcohol misuse.