Genetic, Social, and Developmental Epidemiology of Drug Use Disorders

 描述(由申请人提供)：这一竞争更新的修订寻求继续我们的创新和高生产率的研究计划，目标是利用关于瑞典整个人口的无与伦比的完整性和深度的现有数据，了解药物使用障碍(DUD)的病因、后果和原因。我们有八个具体目标，重点关注哑巴的病因、过程和后果。这些目标是：i)开发一种基于结构方程(SEM)的方法进行相关性分析，然后将其应用于瑞典现有的DUD的关键风险因素，允许对风险因素-DUD关联的程度进行比迄今可能的更严格的评估，该程度是由于家庭混乱和因果关系；II)检查在1951年至1975年出生的所有瑞典男性中，约97%的18岁智商和个性指标预测DUD的强度，并澄清这些关联可能是因果关系的程度；3)探讨120多万名育龄妇女吸烟状况作为护士-助产士报告的一部分，患上糖尿病和吸烟的风险因素的异同；4)利用地理信息系统分析方法，探讨与移民有关的因素如何影响移居瑞典的第一代和第二代移民的哑病风险，重点放在宏观背景特征(即居住隔离)上；五)利用不协调的异性亲属对，阐明哑巴的风险因素如何因性别而异，以及这些风险因素在多大程度上是哑巴特有的，而不是与酒精使用障碍和犯罪的其他关键外在症状共享的；(6)为被领养人、双胞胎、兄弟姐妹、同父异母、典型的非同居父母和继父母制定一个全面的哑巴扫描电子显微镜，以便能够联合估计四个家庭-环境影响来源，利用纵向双胞胎设计检查从青春期到中年的哑巴的遗传和环境风险因素的发育动态，并通过构建纳入广泛遗传和环境风险因素的哑巴的表型-发育扫描电子显微镜模型，澄清从远端到更近端风险因素的关键中介机制；Vii)开发纵向模型以阐明DUD的社会、精神和医学后果，使用相关设计来控制家庭混乱和viii)在潜在和特定的危险因素水平上探索DUD死亡的预测因素，并通过相关性设计澄清这些关联的因果性质。为了实现这些目标，我们将使用瑞典多个全国性数据源的1180万名男性和女性的综合数据。将我们在弗吉尼亚联邦和隆德大学的研究小组在药物滥用研究、社会和遗传流行病学以及因果建模方面的深厚专业知识应用到一个独特的强大样本中，我们预计这项研究将对DUAD研究、预防和政策产生重要影响。

 DESCRIPTION (provided by applicant): This revision of a competitive renewal seeks to continue our innovative and highly productive research program which has the goal of understanding the etiology, consequences and causes of desistance of drug use disorders (DUD) utilizing data available on the entire population of Sweden of unparalleled completeness and depth. We have eight specific aims which focus on the etiology and course and consequences of DUD. These aims are: i) to develop a structural equation (SEM) based approach to co-relative analyses and then apply it to critical risk factors for DUD available in Sweden, permitting a more rigorous assessment than hitherto possible of the degree to which risk factor-DUD associations are due to familial confounding versus causal effects; ii) to examine how strongly DUD is predicted by measures of IQ and personality at age 18 available on ~ 97% of all Swedish males born 1951-1975 and to clarify the degree to which these associations are likely causal; iii) to explore the similarity and differences in risk factors for UD and smoking in over 1.2 million fertile women for whom smoking status is available as part of nurse-midwife's reports; iv) to explore how factors related to immigration, with a focus on macro-level contextual characteristics (i.e., residential segregation), impact risk for DUD among first and second generation immigrants to Sweden using analytical Geographic Information Systems (GIS) methods; v) to clarify how risk factors for DUD vary by gender using discordant opposite-sex relative pairs and the degree to which these risk factors are specific to DUD versus shared with other key externalizing syndromes of alcohol use disorders and crime; vi) to develop a comprehensive SEM for DUD in adoptees, twins, siblings, half-siblings, and typical, not-lived-with and step- parents that will permit joint estimation of four sources of familial-environmental effects, to examine developmental dynamics in the genetic and environmental risk factors for DUD from adolescence to middle age utilizing a longitudinal twin-sibling design and to clarify key mediating mechanisms from distal to more proximal risk factors by constructing a phenotypic-developmental SEM model for DUD that incorporates a wide array of genetic and environmental risk factors; vii) to develop longitudinal models to clarify the social, psychiatric and medical consequences of DUD using co-relative designs to control for familial confounding and viii) to explore the predictors of desistance from DUD on both the latent and specified risk factor level and clarify the causal nature of these associations via co-relative designs. We will use comprehensive data from multiple nationwide data sources in Sweden on 11.8 million men and women to accomplish these goals. Applying the deep expertise of our research groups at Virginia Commonwealth and Lund University in drug abuse research, social and genetic epidemiology and causal modeling to a uniquely powerful sample, we expect this study to have important implications for DUD research, prevention and policy.