Social, Developmental and Epidemiology of Alcohol Use Disorders

项目摘要 我们在这次更新申请中寻求在我们富有成效的第一个项目期间的调查结果的基础上再接再厉 重点是促进我们对风险和保护因素的理解，以及后果， 酒精使用障碍（AUD）。在下一个资助期内，我们将运用我们的流行病学和方法学， 专业知识来检查AUD的以下方面：其表型的病因和后果 异质性;特定因果因素的影响; AUD在夫妻、核心家庭和扩展家系中的传播以及 文化适应对不同移民群体AUD风险的影响。这些目标都利用了广泛的数据 从瑞典的多个全国性数据来源获得的1180万男性和女性的数据，其中26%是 第一代或第二代移民这些数据具有无与伦比的完整性和深度， 已扩展到包括由我们团队创建的瑞典初级保健登记处（PCR）。我们的第一个具体目标 试图通过应用潜在类别分析来解决AUD异质性的重要问题， 在瑞典所有受影响的病例中开发AUD的最佳类型。然后，我们将使用一个半分 设计并确定这些亚型如何与关键风险因素相关联， 与AUD的心理社会和医学后遗症差异相关。我们的第二个目标是使用标准和 新开发的因果推理方法，以检查不良学业成绩对AUD的影响 风险，并评估，在两种不同的方式，有前途的模型，心理传播的澳元内 家庭在这里，我们将利用瑞典注册数据中提供的一系列自然实验。我们的第三个目标 将利用新的PCR和其他医疗登记，以确定时间，遗传， AUD与经典酒精相关医学并发症和 常见的内科疾病，如心血管疾病、高血压和肥胖症。我们的第四个目标是 使用三种主要的方法探索AUD风险在大谱系和婚姻关系中的传播， 策略：先进的SEM方法;在三代家系中探索第二代的特征 将澳元传给第三代的一代成员与不传给第三代的一代成员的比较;以及对 各种婚姻结果可能影响AUD风险和过程的方式。我们的最终目标是 研究，在移民到瑞典，澳元的利率是如何修改的涵化。应用 我们在弗吉尼亚联邦大学和隆德大学的研究小组在澳元研究、社会和经济方面的专业知识 遗传流行病学和因果建模到一个独特的强大的样本，我们将能够提高风险 评估和提供有希望的预防/干预目标的AUD及其后果的见解。

Project Summary We seek, in this revision of our renewal application, to build on the findings of our productive first project period that was focused on advancing our understanding of risk and protective factors for, and the consequences of, Alcohol Use Disorder (AUD). In the next funding period, we will apply our epidemiological and methodological expertise to examine the following facets of AUD: the etiology and consequences of its phenotypic heterogeneity; the influence of specific causal factors; the nature and etiology of the medical consequences of AUD; the transmission of AUD within marital pairs, nuclear families and extended pedigrees and the impact of acculturation on risk for AUD in various immigrant groups. These goals all utilize the wide range of data available from multiple nationwide data sources in Sweden on 11.8 million men and women, 26% of whom are 1st- or 2nd-generation immigrants. These data are of unparalleled completeness and depth and have recently been expanded to include a Swedish primary care registry (PCR) created by our team. Our first specific aim seeks to address the important problem of the heterogeneity of AUD by applying latent class analysis to develop an optimal typology of AUD in all affected cases in Sweden. We will then validate this using a split-half design and determine how these subtypes are associated with key risk factors and whether subtypes are differentially associated with psychosocial and medical sequelae of AUD. Our second aim uses standard and newly developed methods of causal inference to examine the impact of poor academic achievement on AUD risk, and evaluate, in two different ways, promising models for the psychological transmission of AUD within families. We will here utilize a range of natural experiments available in Swedish registry data. Our third aim will capitalize on the newly available PCR and other medical registers to determine the temporal, genetic, and environmental relationships between AUD and both classical alcohol-related medical complications and common medical morbidities such as cardiovascular illness, hypertension and obesity. Our fourth aim will explore the transmission of AUD risk within large pedigrees and marital relationships using three major strategies: advanced SEM methods; exploration within three-generation pedigrees of features of second generation members who do versus do not transmit AUD to the third generation; and study of the multiple ways in which various marital outcomes can impact on the risk for and the course of AUD. Our final aim will examine, among immigrants to Sweden, how rates of AUD are modified by acculturation. Applying the expertise of our research groups at Virginia Commonwealth and Lund University in AUD research, social and genetic epidemiology, and causal modeling to a uniquely powerful sample, we will be able to improve risk assessment and offer insight for promising prevention/intervention targets for AUD and its consequences.