MULTILEVEL INTERPLAYS IN THE DEVELOPMENT OF TOBACCO DEPENDENCE

项目摘要 青少年和年轻人的烟草使用仍然是世界上最具挑战性的公共卫生问题之一。 美国的青少年和青年时期是易受烟草影响的一个窗口期 使用.很大一部分青少年烟草使用者在青少年时期形成烟草依赖， 年轻的成年因此，充分了解烟草依赖的风险机制对于 采取多层次干预措施，以减少烟草依赖的风险。虽然个体水平的遗传 烟草依赖的非遗传风险因素已经建立，只有少数前瞻性研究 评估邻里对吸烟行为的影响。邻域条件和基因的作用- 邻里在烟草依赖的发展中相互作用，特别是在青少年中， 年轻人，还不清楚。此外，作为纵向研究中的常见事件， 邻里接触可能会对吸烟行为产生影响，这在以前的研究中被忽视了。 这可能会导致对邻近效应的不准确估计。密苏里州的青春期女性 双胞胎研究（MOAFTS）是一项特征良好的前瞻性队列研究，其中个体和家庭水平 在基线时收集信息和居住历史，并在20年期间定期更新 跟进。这为我们提供了一个独特的机会来研究邻里关系的主要影响和相互作用 暴露于烟草依赖。具体来说，我们将纵向评估邻里关系的影响， 发展烟草依赖的条件（目标1），并描述 受试者内邻近暴露的变化及其对烟草依赖发展的影响 (Aim 2）。此外，我们将前瞻性地研究邻里接触的相互作用， 遗传易感性对青少年和年轻人烟草依赖风险的影响（目标3）。 国家和全州范围的数据源将用于开发各种小面积邻里措施， 将与MOAFTS队列相关联。通过将边际结构建模与多层次行为建模相结合， 遗传建模，我们将准确地评估邻里和基因邻里相互作用的作用， 烟草依赖通过控制流动性引起的空间不确定性。据我们所知，这将是 第一个前瞻性研究，全面评估邻里条件和基因邻里的作用 在青少年和年轻人的烟草依赖的发展中的相互作用。结果将 完善我们对烟草依赖风险机制的理解，并为多层次战略提供信息， 减少青少年和年轻人的烟草依赖，最终减轻 烟草相关疾病。

PROJECT SUMMARY Tobacco use in adolescents and young adults remains one of the most challenging public health issues in the United States. Adolescence and young adulthood represent a window of heightened vulnerability to tobacco use. A high proportion of adolescent tobacco users develop tobacco dependence during the adolescence and young adulthood. Thus, full understanding of the risk mechanisms of tobacco dependence is critical for multilevel interventions to reduce the risk of developing tobacco dependence. Although individual-level genetic and nongenetic risk factors for tobacco dependence have been established, only few prospective studies have assessed neighborhood effects on smoking behaviors. The role of neighborhood conditions and gene- neighborhood interplays in the development of tobacco dependence, particularly among adolescents and young adults, remain unclear. In addition, as a common event in longitudinal studies, mobility-induced change of neighborhood exposures may have an impact on smoking behaviors, which were ignored in the previous research and might lead to inaccurate estimations of neighborhood effects. The Missouri Adolescent Female Twin Study (MOAFTS) is a well-characterized prospective cohort study in which individual- and family-level information and residential histories were collected at baseline and updated periodically during the 20-year followup. This provides us a unique opportunity to examine the main and interactive effects of neighborhood exposures on tobacco dependence. Specifically, we will longitudinally assess the impacts of neighborhood conditions on the development of tobacco dependence (Aim 1) and characterize the geographic pattern of within-subject changes in neighborhood exposures and its effect on the development of tobacco dependence (Aim 2). Furthermore, we will prospectively examine the interactive effects of neighborhood exposures and genetic predisposition on the risk for tobacco dependence among adolescents and young adults (Aim 3). National and statewide data sources will be used to develop various small-area neighborhood measures that will be linked to the MOAFTS cohort. By integrating marginal structural modeling to multilevel behavioral genetic modeling, we will accurately assess the role of neighborhoods and gene-neighborhood interactions in tobacco dependence by controlling for mobility-induced spatial uncertainty. To our knowledge, this will be the first prospective study to comprehensively assess the role of neighborhood conditions and gene-neighborhood interplays in the development of tobacco dependence among adolescents and young adults. The results will refine our understanding of the risk mechanisms of tobacco dependence and inform multi-level strategies for reducing tobacco dependence among adolescents and young adults, ultimately reducing the burden of tobacco-related diseases.