GENE-NEIGHBORHOOD INTERACTION IN ADOLESCENT AND YOUNG ADULT SMOKING

描述(申请人提供)：吸烟是癌症死亡的首要可预防原因，占美国所有癌症死亡人数的30%以上。尽管吸烟对健康的不利影响受到警告，但美国人中吸烟的流行率仍然很高，特别是在青少年和年轻人中。大多数成年吸烟者在18岁之前就开始吸烟，并在青年时期形成烟草依赖。青少年和年轻人吸烟仍然是最具挑战性的公共卫生问题之一。吸烟行为是高度可遗传的，也受环境的影响。尽管吸烟的遗传和其他个体风险因素已经得到了很好的证实，但很少有研究调查邻里关系对青少年和年轻人吸烟的影响。虽然吸烟的基因-环境相互作用已经得到了广泛的评估，但环境通常侧重于个人或家庭层面的因素。还没有研究调查不利的邻里条件和吸烟的遗传风险因素之间的相互作用。在一个多层次的框架中，对吸烟行为的总体地理差异、吸烟遗传影响的地理异质性以及邻里不利因素对吸烟的影响的修正将能够显著促进改善烟草控制和戒烟干预。基因改变与邻里剥夺相结合，可以通过细分风险级别(风险分层)和改进预防选择来确定干预的目标人群的优先顺序。因此，使用 根据密苏里州青少年女性双胞胎研究(MOAFTS)的数据，我们将探索这样一个假设，即邻里环境改变了遗传倾向对青少年和年轻人吸烟的影响。具体目标有三个：(1)量化青少年和年轻人吸烟的小范围地理差异；(2)确定与青少年和年轻人吸烟有关的社区特征；以及(3)前瞻性地评估不同社区环境对吸烟结果的遗传影响是否有所不同。我们将基于地区层面的数据制定邻里测量，并在收集研究对象的居住地址后将其与MOAFTS数据联系起来，以前瞻性地评估具有遗传倾向的邻里环境对青少年和年轻人吸烟的独立和交互影响。该奖项将允许申请者在吸烟行为的研究方法和行为遗传学方面获得高级技能。本研究结果将为进一步研究R01基因-邻域相互作用机制在吸烟中的作用提供重要支持。在此奖项中获得的培训和研究经验，加上他的指导团队(Mario Schootman博士、Andrew Heath博士、Pamela Madden博士和Graham Colditz博士)的卓越和专业知识，将促进申请者转变为预防吸烟和烟草控制方面的独立学术研究人员。

DESCRIPTION (provided by applicant): Cigarette smoking is the leading preventable cause of cancer mortality and accounts for more than 30% of all cancer deaths in the United States. Despite warnings about its adverse health effects, the prevalence of smoking is still high among US persons, especially among adolescents and young adults. Most adult smokers initiated smoking before age 18 years and developed tobacco dependence during their young adulthood. Adolescent and young adult smoking remains one of the most challenging public health issues. Smoking behaviors are highly-heritable and also influenced by environments. Although genetic and other individual risk factors of smoking have been well established, only few studies examined neighborhood effects on adolescent and young adult smoking. While gene-environment interactions on smoking have been widely evaluated, the environment has been focused typically on individual- or family-level factors. No studies have investigated the interaction between adverse neighborhood conditions and genetic risk factors on smoking. In a multilevel framework, the examination of overall geographic variation in smoking behaviors, geographic heterogeneity of genetic influences on smoking, and effect modification of neighborhood disadvantages on smoking will be able to significantly facilitate improving tobacco control and the intervention in smoking cessation. Genetic alterations combined with neighborhood deprivation could prioritize the target population of the intervention through subdividing the risk levels (risk stratification) and refining prevention choices. Therefore, using the Missouri Adolescent Female Twin Study (MOAFTS) data, we will explore the hypothesis that neighborhood environments modify the influence of genetic predispositions on cigarette smoking among adolescents and young adults. Three specific aims will be addressed: (1) Quantify the small-area geographic variation in adolescent and young adult smoking; (2) Identify neighborhood characteristics that are associated with adolescent and young adult smoking; and (3) Prospectively assess if genetic influences on smoking outcomes vary across distinct neighborhood environments. We will develop neighborhood measures based on area-level data and link them to the MOAFTS data after gecoding the residential addresses of study subjects to prospectively assess the independent and interactive effects of neighborhood environment with genetic predispositions on adolescent and young adult smoking. This award will allow the applicant to gain advanced skills in research methodology and behavioral genetics of smoking behaviors. The findings from the proposed study will provide important support to further investigate gene-neighborhood interplay on smoking through the R01 mechanism. The training and research experience obtained during this award, in combination with the excellence and expertise of his mentoring team (Drs. Mario Schootman, Andrew Heath, Pamela Madden, and Graham Colditz), will promote applicant's transition to an independent academic researcher in smoking prevention and tobacco control.