TOPOGRAPHY AND GENETICS OF SMOKING AND NICOTINE DEPENDENCE IN AMERICAN INDIANS

北方平原美洲印第安人（Al）的终生吸烟率超过50%，是美国人口的两倍多。 在整个美国人口中。更令人担忧的是， 一些阿尔青年。我们的工作表明，Als有一个独特的吸烟模式， 与大多数文化中的吸烟者相比，每天吸烟数量的一半。我们还观察到 最近几代的ALS患者开始吸烟的年龄比过去几代人要小。但很少 严谨的科学研究已经检验了基因和非基因对烟草使用模式的影响 在阿尔斯。从2001年到2007年，我们进行了健康教育和研究（地球）研究， 其中记录了北方平原的EARTH参与者中目前吸烟的流行率为43%， 相比之下西南部落只有19%虽然这些差异可能是多因素的， 这种根本上不同的吸烟流行率的原因是未知的。为了解释这些人口水平 吸烟模式的差异，我们建议检查与吸烟相关的遗传和非遗传因素。 吸烟模式的分层随机抽样的600名成员在原来的地球队列。我们 最重要的假设是，Als对吸烟和尼古丁依赖的易感性与吸烟和尼古丁依赖有关。 潜在的遗传成分，由于与多巴胺、血清素和尼古丁相关的基因变异 新陈代谢，以及心理社会，环境，文化和上下文的影响。所以我们的 具体目标是：1）在已知的吸烟相关基因之间进行候选基因关联研究 多态性和吸烟状况; 2）确定吸烟相关的多态性之间的关联 和尼古丁依赖;和3）检查是否特定的关联模式， 多态性与吸烟状况和尼古丁依赖性的关系因部落而系统地不同。香烟 吸烟是美国可预防死亡的头号原因。拟议的研究将阐明 在两个文化上不同的Al部落群体中，吸烟的原因，最终确定干预目标， 个人和群体水平。通过了解特定的基因型，与非遗传性的 我们可以开始影响吸烟， 可预防的、代价高昂的烟草相关疾病。包括遗传信息是独一无二的研究， 在ALS中的吸烟行为，并可能在制定吸烟预防和戒烟计划中发挥作用 在个人和社区层面。考虑到部落土地上烟草销售的独特法律， 调查结果可能会对方案和政策相关的公共卫生产生各种影响。

Lifetime smoking prevalence in Northern Plains American Indians (Al) is above 50%, more than double the rate in the overall U.S. population. More worrisome is that smoking prevalence is actually increasing among some Al youth. Our work demonstrates that Als have a unique pattern of smoking, with Als typically smoking one-half the number of cigarettes per day compared with smokers in the majority culture. We also observed that more recent generations of Als are initiating smoking at younger ages than in past generations. Yet few rigorous scientific studies have examined the genetic and non-genetic influences on patterns of tobacco use in Als. From 2001 to 2007, we conducted the Education and Research Towards Health (EARTH) study, which documented the prevalence of current smoking among Northern Plains' EARTH participants was 43%, compared to only 19% in the Southwest tribe. Although these differences are likely multi-factorial, the reasons for such radically, different smoking prevalences are unknown. To explicate these population-level differences in smoking patterns, we propose to examine the genetic and non-genetic factors associated with cigarette smoking patterns in a stratified random sample of 600 members in the original EARTH cohort. Our overarching hypothesis is that the susceptibility of Als to smoking and nicotine dependence has an underlying genetic component, due to gene variants related to dopamine, serotonin, and nicotine metabolism, as well as psychosocial, environmental, cultural, and contextual influences. Therefore, our specific aims are to: 1) Perform candidate-gene association studies between known smoking-related polymorphisms and smoking status; 2) Determine the association between smoking-related polymorphisms and nicotine dependence among smoker; and 3) Examine whether the pattern of association of specific polymorphisms with smoking status and nicotine dependence varies systematically by tribe. Cigarette smoking is the number 1 cause of preventable death in the U.S.^¿ The proposed research will illuminate the causes of smoking in 2 culturally distinct Al tribal groups, ultimately to identify targets for intervention at the individual and population levels. By understanding how particular genotypes, in concert with non-genetic factors, predispose some Al tribal groups to smoking, we can begin to affect smoking and the multitude of preventable and costly tobacco-related diseases. Including genetic information is unique in studies of smoking behaviors among Als, and may have a role in shaping smoking prevention and cessation programs at the individual and community level. Given the unique laws governing tobacco sales on tribal lands, our findings could have a myriad of programmatic and policy-related public health impacts.