Social, Developmental and Genetic Epidemiology of Alcohol Use Disorders

描述(由申请人提供)：尽管遗传和环境因素对酒精使用障碍(AUD)都有重要作用，但我们对家庭、同伴和邻里环境之间的动态和因果关系以及在AUD发展过程中的遗传风险的了解仍然有限。为了进一步了解特定的社会和遗传因素对AUD的影响，我们建议从生命过程的角度来提高对原因机制的认识。我们的具体目标是：评估邻里环境、同辈背景和家庭制度在敏感发育时期的生命过程中的影响，并检查邻里环境的累积影响(使用消除同源偏见的客观措施)；理清压力(不利环境导致AUD)和漂移(AUD导致社会向下流动)假说；检验人口亚群中的中介(风险链)和影响修饰者；区分家庭水平的环境和遗传对AUD的影响；以及确定遗传风险因素对环境逆境致病效应的敏感性程度。我们建议使用来自瑞典多个全国性数据源的综合数据。这将使我们能够评估从1970年开始对整个瑞典人口的累积邻里接触情况，并对澳元进行后续分析，直至2010年。我们的数据库将包含1180万男女的全国数据，他们的居住社区是根据社会(例如剥夺、犯罪)和身体(酒精供应)因素进行地理编码和定义的。在谨慎的道德保障下，国家登记处允许我们通过连接人口普查数据、家庭关系数据、邻里层面的社会和自然环境记录、犯罪数据、应征入伍士兵数据、死因记录、住院和门诊记录以及所有处方药记录来构建数据库。AUD的诊断从1973年开始，个人和邻居层面的因素从1970年开始。我们将使用潜在的班级增长模型和边际结构模型来考虑个人流动性和社区随时间的变化。我们将使用倾向得分匹配和相关对照设计来控制选择性迁移，从而提高确定因果关系的能力。此外，我们将利用先进的地理信息系统分析技术对邻近地区的暴露进行精细评估，并研究基因与环境的相互作用，这将通过综合遗传学和环境跨学科方法为政策干预和健康促进提供更有力的基础。将我们在人类发展以及社会和遗传流行病学方面的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AUD的研究、预防和政策产生重要影响。

DESCRIPTION (provided by applicant): Despite the importance of both genetic and environmental contributions to alcohol use disorders (AUD), we still have limited knowledge about the dynamic and causal relationships between family, peer and neighborhood contexts and genetic risks in the development of AUD over the life course. To further our understanding of specific social and genetic effects on AUD, we propose to take a life course perspective to improve knowledge of causal mechanisms. Our specific aims are: to assess effects of the neighborhood environment, peer context and family system over the life course during sensitive developmental periods and examine the accumulated impact of neighborhood environments (using objective measures that eliminate same-source bias); to disentangle the stress (adverse environments cause AUD) vs. drift (AUD cause downward social mobility) hypotheses; to examine mediators (chains of risk) and effect modifiers in population subgroups; to distinguish family-level environment and genetic effects on AUD; and to determine the degree to which genetic risk factors moderate sensitivity to the pathogenic effects of environmental adversity. We propose to use comprehensive data from multiple nationwide data sources in Sweden. This will allow us to assess cumulative neighborhood exposures beginning in 1970 for the entire Swedish population and to conduct follow-up analyses of AUD until 2010. Our database will contain nationwide data on 11.8 million men and women whose neighborhoods of residence are geocoded and defined based on social (e.g. deprivation, crime) and physical (alcohol availability) factors. With careful ethical safeguards, national registries permit us to construct database by linking census data, family relationship data, neighborhood-level social and physical environmental records, crime data, military conscript data, cause of death records, inpatient and outpatient hospital records, and all prescription medication records. AUD diagnoses are available beginning in 1973 and individual- and neighborhood-level factors beginning in 1970. We will account for individual mobility and neighborhood change over time by using latent class growth modeling and marginal structural models. We will use propensity score matching and co- relative control designs to control for selective migration and thereby improve the ability to determine causality. Furthermore, we will produce refined assessments of neighborhood exposures from advanced GIS analytic techniques and study gene-environment interactions, which will provide a more robust basis for policy interventions and health promotion via an integrated genetics and environmental cross-disciplinary approach. Applying our expertise in human development and social and genetic epidemiology to a uniquely powerful sample, we expect this study to have important implications for AUD research, prevention and policy.