Neighborhoods and Coronary Disease: Exploring Mechanisms and Improving Methods

描述(由申请人提供)：背景：以前的研究为更详细地研究邻里效应对冠心病(CHD)的因果机制提供了理由。目的：从生命过程的角度进一步了解社区对冠心病相关结局的影响，提高对病因机制的认识，并通过遗传学和环境跨学科的综合方法为政策干预和健康促进提供更有力的基础。具体目标：考察社区社会环境(例如社区富裕/贫困、社区安全/犯罪、社会资本)和社区物理环境(使用社区商品、服务和资源的客观衡量标准)随时间对冠心病事件以及代谢和行为冠心病危险因素的累积影响。检验群体亚组中的调节因子和效应调节因子。研究遗传变异(SNPs)与冠心病发病和冠心病危险因素以及邻里社会和自然环境之间的基因-环境相互作用。设计/方法：我们将使用两个新的数据库，地理信息系统(GIS)-环境数据库和冠状动脉风险数据库，这两个数据库基于瑞典多个全国来源的综合数据集。这将使我们能够评估从1970年开始的累积邻里接触情况：1)整个瑞典人口；2)基于人群的队列(包括生物库和基因数据)；并对CHD相关结果进行跟踪分析，直到2016年。我们的新的冠状动脉风险数据库包含1180万男女的全国数据，他们的居住社区已进行地理编码；新的地理信息系统环境数据库包含关于整个瑞典超过25万种地理编码的商品、服务和资源的历史和当前信息。瑞典所有人都有一个已被序列号取代的个人识别码，用于建立数据库，方法是将人口普查数据、社区一级的社会和自然环境记录、死因记录、住院和门诊记录以及所有处方药记录联系起来。冠心病的诊断从1985年(住院患者)和2001年(门诊患者)开始，从1970年开始个人和邻居层面的因素。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基于家庭的设计来控制选择性迁移，从而与以前的研究相比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社区暴露进行精细评估，并研究常见遗传变量(SNPs)与可能影响CHD的社区社会和自然环境之间的相互作用，后者通过探索性的全环境关联研究进行。

DESCRIPTION (provided by applicant): Background: Previous studies have provided justification for more detailed investigations of causal mechanisms behind the neighborhood effect on coronary heart disease (CHD). Objectives: To further our understanding of specific neighborhood effects on CHD-related outcomes in a life-course perspective, improve knowledge of causal mechanisms, and provide a more robust basis for policy interventions and health promotion via an integrated genetics and environmental cross-disciplinary approach. Specific aims: To examine the accumulated impact of neighborhood social environments (e.g., neighborhood affluence/deprivation, neighborhood safety/criminality, social capital) and neighborhood physical environments (using objective measures of neighborhood goods, services, and resources) over time on incident CHD as well as metabolic and behavioral CHD risk factors. To examine mediators and effect modifiers in population subgroups. To examine gene-environment interactions between genetic variants (SNPs) in relation to incident CHD and CHD risk factors and neighborhood-level social and physical environments. Design/methods: We will use two new databases, the Geographic Information System (GIS)-Environment Database and the Coronary Risk Database, that are based on comprehensive datasets from multiple nationwide sources in Sweden. This will allow us to assess cumulative neighborhood exposures beginning in 1970 for: 1) the entire Swedish population, and 2) population-based cohorts (including biobanks and genetic data); and conduct follow-up analyses of CHD-related outcomes until 2016. Our new Coronary Risk Database contains nationwide data on 11.8 million men and women whose neighborhoods of residence are geocoded; the new GIS- Environment Database contains historical and current information on more than 250,000 geocoded goods, services and resources in all of Sweden. All persons in Sweden have a personal identification number that has been replaced by a serial number and used to construct the databases by linking census data, neighborhood- level social and physical environmental records, cause of death records, inpatient and outpatient hospital records, and all prescription medicine records. CHD diagnoses are available beginning in 1985 (inpatient) and 2001 (outpatient), 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 family-based designs to control for selective migration and thereby improve the ability to determine causality compared to previous research. Furthermore, we will produce refined assessments of neighborhood exposures from advanced GIS analytic techniques and study interactions between common genetic variants (SNPs) and neighborhood social and physical environments that may influence CHD, the latter by using an exploratory Environment-Wide Association Study.