A genetically informative approach to understanding the impact of spousal psychiatric disorders on alcohol use disorder onset, remission, and relapse

项目摘要 我们在这个新的R01提案中的目标是描述配偶的药物使用和精神疾病的影响 其配偶的酒精使用障碍(AUD)在婚姻期间的发病、缓解和复发 遗传信息框架。到目前为止，了解配偶对酒精结果的影响的努力已经 主要关注酒精特有的传染模型，根据该模型，一个伴侣的酒精使用行为是 通过社交传播给另一个人。然而，鉴于以下原因，这种针对酒精的特定传染病是有限制性的 流行病学证据表明，受AUD影响的个人的配偶也往往患有其他常见疾病 精神障碍，包括严重抑郁障碍、广泛性焦虑症、其他药物滥用/依赖、 多动症和反社会人格障碍。我们以这些流行病学发现为基础来澄清 这些其他形式的配偶药物使用与精神障碍和关键 酒精结果包括AUD的发病、缓解和复发。我们在遗传信息丰富的情况下这样做 框架，也认识到配偶的遗传倾向对疾病的潜在贡献，甚至 在没有诊断(即社会遗传效应)的情况下，以及焦点个体的基因如何可能 使他/她对配偶的疾病(即，基因-环境相互作用的影响)有不同的敏感性。相关 这个二次数据分析项目的表型和基因数据来自配偶二人组(N=1,688 作为NIAAA资助的酒精中毒遗传学合作研究(COGA)的一部分收集的。我们的 具体目标是：(1)描绘配偶物质之间潜在的时间动态 使用和精神障碍诊断(包括大麻使用障碍、其他精神活性药物使用 精神障碍、反社会个人障碍、多动症、尼古丁依赖、严重抑郁障碍和创伤后应激障碍)以及 他们的伴侣的澳门氏症的发病、缓解和复发；(2)确定配偶的遗传倾向 精神障碍(除了诊断本身之外)与其伴侣的AUD发病有关， 缓解和复发；(3)检查局部个体对酒精问题的遗传易感性 预测他们对配偶药物使用和精神障碍的敏感度的变异性；以及(4)评估 预期效果是否随性和为人父母的不同而不同。这一结果可能具有理论上的 扩展AUD的社会压力模型以包括配偶药物使用和精神疾病的影响 精神障碍，反过来，这一知识预计将对夫妇和基于家庭系统的 澳大利亚糖尿病的预防性干预措施。更广泛地说，这项工作将有助于合作研究团队的 长期目标是阐明遗传因素和密切关系因素如何共同影响 房缺的发病、持续和间断。

Project Summary Our objective in this new R01 proposal is to delineate the impact of a spouse’s substance use and psychiatric disorders on their partner’s alcohol use disorder (AUD) onset, remission, and relapse during marriage within a genetically informative framework. To date, efforts to understand spousal influences on alcohol outcomes have largely focused on alcohol-specific contagion models, whereby alcohol use behaviors in one partner are socially transmitted to the other. Yet, this prior focus alcohol-specific contagion is restrictive in view of epidemiological evidence that spouses of AUD-affected individuals also tend to suffer from other common disorders, including major depressive disorder, generalized anxiety disorder, other drug abuse/dependence, ADHD, and antisocial personality disorder. We build on these epidemiological findings to clarify the nature of the associations between these other forms of spousal substance use and psychiatric disorders and key alcohol outcomes including AUD onset, remission, and relapse. We do this within a genetically informative framework that also recognizes the potential contributions of a spouse’s genetic propensity for a disorder even in the absence of a diagnosis (i.e., social genetic effects), as well as how the focal individual’s genotype may differentially sensitize him/her to a spouse’s disorder (i.e., gene-environment interaction effects). Relevant phenotypic and genotypic data for this secondary data analysis project come from spousal dyads (N = 1,688 dyads) collected as part of the NIAAA-funded Collaborative Study on the Genetics of Alcoholism (COGA). Our specific aims are to: (1) Delineate the temporal dynamics underlying associations between spousal substance use and psychiatric disorder diagnoses (inclusive of cannabis use disorder, other psychoactive drug use disorder, antisocial personal disorder, ADHD, nicotine dependence, major depressive disorder, and PTSD) and their partner’s AUD onset, remission, and relapse; (2) Identify whether a spouse’s genetic propensity for psychiatric disorders (above and beyond a diagnosis itself) is associated with their partner’s AUD onset, remission, and relapse; (3) Examine whether the focal individual’s genetic predisposition for alcohol problems predicts variability in their sensitivity to spousal substance use and psychiatric disorders; and (4) Evaluate whether the expected effects differ as a function of sex and parenthood. The results may have theoretical implications for expanding social stress models of AUD to include spousal substance use and psychiatric disorders, and in turn this knowledge is anticipated to have implications for couples and family systems-based preventive interventions for AUD. More broadly, this work will contribute to the collaborative research team’s long-term goal to elucidate how genetic factors and close relationship factors come together to influence the onset, persistence, and discontinuity of AUD.