Genetic and Environmental Risks for Smoking Characteristics and Cessation

吸烟特征和戒烟的遗传和环境风险

• 批准号: 8325014
• 负责人: Li-Shiun Chen
• 金额: $ 16.78万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8325014
• 关键词: Abstinence; Accounting; Affect; African American; Award; Behavioral; Biological; Cessation Research; Characteristics; Cigarette; Clinical; Comorbidity; Country; DSM-IV; Data; Data Analyses; Data Collection; Data Set; Dependence; Development; Diagnosis; Diagnostic and Statistical Manual; Disease; Environment; Environmental Risk Factor; Epidemiology; Equipment and supply inventories; Etiology; European; Family; Follow-Up Studies; Foundations; Future; General Population; Genetic; Genetic Predisposition to Disease; Genetic Risk; Goals; Hand; Health Care Costs; Heritability; Knowledge; Link; Literature; Measures; Mental disorders; Methods; Morbidity - disease rate; Nicotine Dependence; Outcome; Outcomes Research; Phenotype; Population; Prevention; Probability; Prospective Studies; Psychiatrist; Public Health; Relapse; Research; Research Methodology; Research Personnel; Research Training; Rice; Sampling; Science; Smoker; Smoking; Smoking Behavior; Syndrome; Testing; Time; Tobacco; Training; Transdisciplinary Tobacco Research Center; Translating; Treatment Factor; Universities; Variant; Washington; Wisconsin; Withholding Treatment; Work; career; cigarette smoking; economic cost; experience; follow-up; genetic association; genetic variant; genome wide association study; innovation; insight; mortality; novel; peer; programs; prospective; psychogenetics; smoking cessation; success; treatment strategy

DESCRIPTION (provided by applicant): I request support through the K08 award to complete my transition from a clinical board-certified psychiatrist with prior research training in epidemiology to an independent translational researcher in genetic and environmental factors for smoking cessation. To achieve this goal, I need further training and experience in advanced genetics, cessation science, and longitudinal research methods, to enable me to conduct future prospective studies on genetics of smoking cessation. I will be guided by experts in the fields of advanced genetics (Drs. Laura Bierut, Alison Goate, John Rice, and Robi Mitra), cessation science (Drs. Timothy Baker and Gary Swan), and longitudinal research (Drs. Naomi Breslau, Eric Johnson, Laura Bierut, and Timothy Baker). The training goals will be advanced through the following proposed research on nicotine dependence which is a serious public health problem. Some genetic variants associated with nicotine dependence and smoking cessation have been identified with modern genetic methods, but account for only a small amount of genetic variance. Our preliminary results suggest comprehensive nicotine dependence phenotypes and prospective cessation measures have greater sensitivity to detect genetic associations. This study aims to fill gaps in the research literature by conducting (1) Genome Wide Association Study (GWAS) analyses of nicotine dependence using comprehensive novel phenotypes in two existing, complementary datasets (population vs. treatment sample), (2) GWAS analyses of prospective smoking cessation phenotype, and (3) a pilot longitudinal follow up study of nicotine dependence subjects to replicate the genetic findings of smoking cessation from study aim 2, and to examine identified genetic risks jointly with environmental, comorbid, and treatment factors. We hope to uncover novel genetic variants associated with refined phenotypic characteristics of nicotine dependence and smoking cessation. Genetic risks associated with smoking cessation may be different from those for nicotine dependence, and this distinction will be useful in translating genetic risk to outcome research. Knowledge of how genetic risks influence clinical outcomes and whether they are modified by treatment and comorbid disorder factors will not only clarify the etiology of nicotine dependence to create opportunity for prevention, but also provide needed evidence for individualized cessation treatments to increase the probability of successful quitting. This will be the foundation for future R01 applications for large scale, prospective studies of smoking cessation trials. In summary, by the end of this award, I will become an expert in psychiatric genetics with a focus on smoking cessation. Through my training in advanced genetic methods, cessation science, and longitudinal analyses, along with hands on experience in longitudinal data collection and analyses, I will establish a unique smoking cessation research program at Washington University and launch an independent career conducting large scale smoking cessation trials that will make important contributions to the treatment of nicotine dependence and related disorders.

描述（由申请人提供）：我请求通过 K08 奖获得支持，以完成我从接受过流行病学研究培训的临床委员会认证精神科医生到戒烟遗传和环境因素独立转化研究员的转变。为了实现这个目标，我需要在先进的遗传学、戒烟科学和纵向研究方法方面进一步的培训和经验，使我能够在未来进行戒烟遗传学的前瞻性研究。我将得到先进遗传学领域（Laura Bierut 博士、Alison Goate、John Rice 和 Robi Mitra 博士）、戒烟科学（Timothy Baker 博士和 Gary Swan 博士）和纵向研究（Naomi Breslau 博士、埃里克·约翰逊、劳拉·比鲁特和蒂莫西·贝克）。培训目标将通过以下拟议的尼古丁依赖研究来推进，尼古丁依赖是一个严重的公共卫生问题。现代遗传学方法已经鉴定出一些与尼古丁依赖和戒烟相关的遗传变异，但只解释了少量的遗传变异。我们的初步结果表明，综合尼古丁依赖表型和前瞻性戒烟措施对检测遗传关联具有更高的敏感性。本研究旨在通过以下方式填补研究文献中的空白：(1) 使用两个现有互补数据集（人群与治疗样本）中的综合新表型对尼古丁依赖进行全基因组关联研究 (GWAS) 分析，(2) 对尼古丁依赖性进行 GWAS 分析。前瞻性戒烟表型，以及（3）对尼古丁依赖受试者进行一项试点纵向随访研究，以复制研究目标 2 中戒烟的遗传发现，并与环境、环境等因素联合检查已确定的遗传风险。合并症和治疗因素。我们希望发现与尼古丁依赖和戒烟的精细表型特征相关的新的遗传变异。与戒烟相关的遗传风险可能与尼古丁依赖相关的遗传风险不同，这种区别将有助于将遗传风险转化为结果研究。了解遗传风险如何影响临床结果以及它们是否会因治疗和共病疾病因素而改变，不仅可以阐明尼古丁依赖的病因，为预防创造机会，而且还可以为个体化戒烟治疗提供所需的证据，以提高成功戒烟的可能性。这将为未来 R01 应用于大规模、前瞻性戒烟试验研究奠定基础。总之，到这个奖项结束时，我将成为专注于戒烟的精神遗传学专家。通过我在先进遗传方法、戒烟科学和纵向分析方面的培训，以及纵向数据收集和分析方面的实践经验，我将在华盛顿大学建立一个独特的戒烟研究项目，并开始进行大规模戒烟试验的独立职业生涯这将为尼古丁依赖及相关疾病的治疗做出重要贡献。