Social, Developmental and Genetic Epidemiology of Alcohol Use Disorders

描述（由申请人提供）：尽管遗传和环境对酒精使用障碍（AUD）的影响都很重要，但我们对家庭、同伴和社区环境以及在生命过程中AUD发展中的遗传风险之间的动态和因果关系的了解仍然有限。为了进一步了解AUD的具体社会和遗传影响，我们建议从生命历程的角度来提高对因果机制的认识。我们的具体目标是：评估社区环境、同伴环境和家庭系统在敏感发育时期的生命历程中的影响，并检查社区环境的累积影响（使用消除同源偏差的客观测量）；厘清压力（不利环境导致AUD）与漂移（AUD导致向下的社会流动性）假说；在人群亚组中检查调节因子（风险链）和效果调节因子；区分家庭层面的环境和遗传对AUD的影响；并确定遗传危险因素对环境逆境致病效应的中等敏感程度。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整个瑞典人口从1970年开始的累积邻里暴露情况，并对澳元进行随访分析，直到2010年。我们的数据库将包含全国1180万男性和女性的数据，这些男性和女性的居住社区是地理编码的，并根据社会（如贫困、犯罪）和物理（可获得酒精）因素进行定义。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、社区一级的社会和物理环境记录、犯罪数据、军事征召数据、死因记录、住院和门诊医院记录以及所有处方药记录来构建数据库。1973年开始有AUD诊断，1970年开始有个体和社区水平的因素。我们将使用潜在阶级增长模型和边际结构模型来解释个人流动性和社区随时间的变化。我们将使用倾向评分匹配和相关控制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GIS分析技术对社区暴露进行精细评估，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坚实的基础。将我们在人类发展、社会和遗传流行病学方面的专业知识应用于一个独特的强大样本，我们希望这项研究对AUD的研究、预防和政策具有重要意义。

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.