Social, Developmental and Epidemiology of Alcohol Use Disorders

项目摘要 我们希望，在我们的续签申请的这次修订中，以我们富有成效的第一个项目期的调查结果为基础 重点是促进我们对风险和保护因素以及其后果的理解， 酒精使用障碍(AUD)。在下一个资助期，我们将运用我们的流行病学和方法学 检查AUD的以下方面的专业知识：其表型的病因和后果 异质性；特定原因的影响；医疗后果的性质和病因 AUD；AUD在婚姻配对、核心家庭和大家族中的传播及其影响 不同移民群体对澳元病风险的适应。这些目标都利用了广泛的数据 可从瑞典的多个全国性数据来源获得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，最近 已扩展到包括由我们团队创建的瑞典初级保健登记处(PCR)。我们的第一个明确目标 寻求通过应用潜在类别分析来解决AUD的异质性这一重要问题 制定瑞典所有受影响病例的最佳AUD类型。然后，我们将使用一分为二的方法进行验证 设计并确定这些子类型如何与关键风险因素相关联，以及子类型是否 与AUD的心理社会和医学后遗症有不同的关联。我们的第二个目标是使用标准和 检验学业成绩差对AUD影响的新因果推理方法 风险，并以两种不同的方式评估有希望的澳元内部心理传导模型 家人。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 将利用最新可用的聚合酶链式反应和其他医学登记来确定时间、遗传和 AUD与经典酒精相关医疗并发症和 常见的医学疾病，如心血管疾病、高血压和肥胖。我们的第四个目标是 利用三个主要因素探讨AUD风险在大家系和婚姻关系中的传递 策略：先进的扫描电子显微镜方法；在三代家系内探索第二代的特征 与不将AUD传递给第三代的世代成员；以及倍数的研究 不同的婚姻结局如何影响澳门氏症的风险和病程。我们的最终目标是 考察移居瑞典的移民的澳元比率如何因文化适应而改变。应用 我们在弗吉尼亚联邦和隆德大学的研究小组在AUD研究、社会和 遗传流行病学和因果建模到一个独特的强大样本，我们将能够提高风险 评估并为有前景的澳门氏症预防/干预目标及其后果提供洞察力。

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.