GENE-NEIGHBORHOOD INTERACTION IN ADOLESCENT AND YOUNG ADULT SMOKING

描述（由申请人提供）：吸烟是癌症死亡的主要可预防原因，占美国所有癌症死亡的30%以上。尽管对吸烟有害健康的影响提出了警告，但吸烟在美国人中的流行率仍然很高，特别是在青少年和年轻人中。大多数成年吸烟者在18岁之前开始吸烟，并在年轻时形成烟草依赖。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。吸烟行为具有高度遗传性，也受环境影响。虽然吸烟的遗传和其他个体风险因素已经得到了很好的建立，但只有少数研究探讨了青少年和年轻人吸烟的邻居效应。虽然吸烟的基因-环境相互作用已被广泛评估，但环境通常集中在个人或家庭层面的因素上。没有研究调查不良的邻里条件和吸烟的遗传风险因素之间的相互作用。在多水平框架下，研究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社区不利因素对吸烟的影响，将有助于改善烟草控制和戒烟干预。遗传改变与邻里剥夺相结合，可以通过细分风险水平（风险分层）和改进预防选择来优先考虑干预的目标人群。因此用 密苏里州青少年女性双胞胎研究（MOAFTS）的数据，我们将探讨这一假设，即邻里环境改变的影响，遗传易感性对吸烟的青少年和年轻人。将解决三个具体目标：（1）量化青少年和年轻人吸烟的小区域地理差异;（2）识别与青少年和年轻人吸烟相关的社区特征;（3）Prophylaxis评估遗传对吸烟结果的影响是否在不同的社区环境中存在差异。我们将根据区域层面的数据制定社区措施，并在对研究对象的居住地址进行编码后将其与MOAFTS数据联系起来，以前瞻性地评估具有遗传倾向的社区环境对青少年和年轻人吸烟的独立和互动影响。该奖项将使申请人获得先进的研究方法和吸烟行为的行为遗传学技能。这项研究的结果将为进一步研究R 01基因与邻近基因的相互作用机制提供重要支持。在此期间获得的培训和研究经验，结合他的指导团队（Mario Schootman博士，Andrew Heath博士，Pamela Madden博士和Graham科迪茨博士）的卓越和专业知识，将促进申请人过渡到吸烟预防和烟草控制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.