Genetic, Social, and Developmental Epidemiology of Drug Use Disorders

 描述（由申请人提供）：本次竞争性更新的修订旨在继续我们的创新和高产研究计划，该计划的目标是利用瑞典整个人口的数据，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，重点是DUD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）的相关分析方法，然后将其应用于瑞典现有的DUD关键风险因素，从而能够比迄今为止更严格地评估风险因素-DUD关联的程度是由于家族混杂效应还是因果效应; ii）研究1951年出生的所有瑞典男性中约97%的人在18岁时的智商和个性指标对DUD的预测能力有多强-1975年，并澄清这些协会可能是因果关系的程度; iii）探索的相似性和差异的风险因素UD和吸烟在超过120万生育妇女的吸烟状况是可作为护士助产士的报告的一部分;（四）探讨与移民有关的因素，重点是宏观层面的背景特征（即，居住隔离），使用分析地理信息系统（GIS）方法在瑞典的第一代和第二代移民中对DUD的影响风险; v）使用不一致的异性亲属对，澄清DUD的风险因素如何因性别而异，以及这些风险因素对DUD特有的程度与其他酒精使用障碍和犯罪的关键外部综合征的共享程度; vi）在被收养者、双胞胎、兄弟姐妹、同父异母兄弟姐妹和典型的、不与父母生活在一起的和继父母中开发一个全面的DUD SEM，该SEM将允许联合估计家庭环境影响的四个来源，利用纵向双胞胎研究从青春期到中年DUD的遗传和环境风险因素的发展动态，同胞设计，并通过构建DUD的表型-发育SEM模型，阐明从远端到近端风险因素的关键介导机制，该模型包含广泛的遗传和环境风险因素; vii）开发纵向模型，以澄清社会，DUD的精神和医学后果，使用相关设计来控制家族性混杂因素，以及viii）探索潜在和特定风险因素水平上终止DUD的预测因素，并通过相关设计阐明这些关联的因果性质。我们将利用来自瑞典全国多个数据来源的1180万男女的综合数据来实现这些目标。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于一个独特而强大的样本，我们预计这项研究将对DUD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.