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

项目摘要 本提案的目的是促进对父母通过其 离婚/分居和婚姻不和影响后代酒精使用障碍（AUD）和相关结果 (e.g.,第一次饮酒的年龄和酒精滥用）。人们普遍认为，父母离婚/分居和 父母婚姻不和对后代酒精结果有直接的致病影响。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，尽管有暗示性证据表明， 暴露于父母婚姻问题的人也会遗传AUD遗传倾向， 易患体质可使个体对环境压力的不利影响敏感。这突出表明 需要研究遗传因素和这些常见的家庭逆境的汇合，以了解他们的 关于后代酒精结果的共同遗产。这里的目标是使用来自两个国家的数据来解决这一差距。 跨代的，基因信息研究。第一个是弗吉尼亚州成人双胞胎精神病学研究， 物质使用障碍，从出生时招募的欧洲血统双胞胎样本（N=9345，45%女性） 对所有双胞胎和一部分父母进行直接精神病学访谈的记录 （N=1472，58%女性），通过诊断性精神病家族史收集额外的父母数据 采访双胞胎。第二个是酒精中毒遗传学的合作研究（N=11561，53% 女性），一项针对不同种族（69%欧洲裔美国人，31%非洲裔美国人）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，这些先证者的精神病学访谈数据 收集所有参与者。这两个样本是相互提供信息，允许检查 不同方法和人群的结果的普遍性和趋同性。以一种生物学的方式， 生态框架，目的是：（1）检查在何种程度上，父母之间的关联 离婚/分居、父母婚姻不和和后代酒精结果反映了直接的（即，'causes'）效应 与共享的遗传效应;（2）检查后代遗传因素是否预测其遗传变异性。 对父母离婚/分居和父母婚姻不和的反应。结果可能具有理论上的 间接的，环境途径的影响，通过这些途径，酒精问题的遗传风险是 在家庭中传播（即，基因与环境的相关性），以及对基因 影响赋予对家族性紧张性刺激的敏感性（即，基因-环境相互作用）。反过来，结果可能 告知临床医生心理教育工作，以防止家庭后代滥用酒精 经历婚姻危机和离婚更广泛地说，这项工作将有助于实现联合国千年发展目标的长期目标。 早期研究者PI的研究计划，以描绘遗传因素和密切关系 各种因素共同影响酒精滥用的发生、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.