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

使用遗传信息设计来了解父母离婚/分居和父母婚姻不和对后代酗酒结果的影响

• 批准号: 10460823
• 负责人: JESSICA E SALVATORE
• 金额: $ 31.55万
• 依托单位: RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-05 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10460823
• 关键词: Address; Adult; Adverse effects; African American; Age; Alcohol abuse; Alcohol consumption; Alcohols; American; Archives; Behavior; Birth Records; Clinical; Complex; Data; Data Set; Diagnostic; Distress; Divorce; Environment; Etiology; European; Exposure to; Family; Female; Funding; Genes; Genetic; Genetic Predisposition to Disease; Genetic Risk; Genetic study; Goals; Heritability; Individual; Inherited; Intervention; Interview; Joints; Methods; Mission; Modeling; Molecular Genetics; Nature; Onset of illness; Outcome; Parents; Participant; Pathogenicity; Pathway interactions; Population; Predictive Factor; Public Health; Recording of previous events; Research; Research Personnel; Risk; Role; Sampling; Skin; Stress; Substance Use Disorder; Suggestion; Testing; Twin Multiple Birth; Twin Studies; United States National Institutes of Health; Virginia; Work; alcohol misuse; alcohol misuse prevention; alcohol related problem; alcohol use disorder; childhood adversity; cost; design; divorce/separation; environmental stressor; ethnic diversity; experience; gene environment interaction; genetics of alcoholism; high risk; intergenerational; intervention program; novel; offspring; population based; proband; programs; psychoeducation; recruit; response; social; stressor; tool

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.

项目概要 该提案的目的是增进对父母教育机制的理解。 离婚/分居和婚姻不和会影响后代酒精使用障碍（AUD）和相关结果 （例如，首次饮酒的年龄较早和酗酒）通常被认为是父母离婚/分居和酗酒的结果。 父母婚姻不和对后代酗酒有直接的致病影响，但影响有限。 尽管有暗示性证据表明后代 暴露于父母婚姻问题也会遗传 AUD 遗传倾向，并且 AUD 遗传 易感性可以使个体对环境压力源的不利影响敏感。 需要研究遗传因素和这些常见的家庭逆境的综合作用，以了解他们的情况 这里的目标是使用两个数据来解决这一差距。 第一个是弗吉尼亚成人双胞胎精神病学和遗传信息研究。 物质使用障碍，从出生起就招募的欧洲血统双胞胎样本（N = 9345，45% 女性） 收集了所有双胞胎以及部分父母的直接精神病学访谈数据的记录 （N=1472，58% 女性），通过诊断精神病家族史收集额外的父母数据 第二个是对双胞胎的访谈（N=11561，53%）。 女性），针对不同种族（69% 欧洲裔美国人，31% 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，针对这些先证者的精神病学访谈数据 从所有参与者收集的这两个样本在允许检查方面相互提供信息。 在生物指导下，不同方法和人群的研究结果具有普遍性和趋同性。 生态框架，目标是：（1）检查父母之间的关联程度 离婚/分居、父母婚姻不和以及后代酗酒结果反映了直接（即“因果”）影响 (2) 检查后代遗传因素是否预测变异性与共享遗传效应；以及 (2) 检查后代遗传因素是否预测其遗传效应； 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意义。 对酒精问题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），以及对遗传如何进行的理解 影响赋予对家庭压力源的敏感性（即基因-环境相互作用）。 告知圣徒的心理教育工作，以防止家庭后代滥用酒精 更广泛地说，这项工作将有助于实现婚姻困境和离婚。 早期研究者 PI 的研究计划旨在描述遗传因素和密切关系如何影响 多种因素共同影响酒精滥用的发生、持续和中断。