Gene-Gene/Gene-Environment Interactions Associated with Nicotine Dependence

与尼古丁依赖相关的基因-基因/基因-环境相互作用

• 批准号: 8443232
• 负责人: Qing Lu
• 金额: $ 17.52万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-02-15 至 2018-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8443232
• 关键词: Accounting; Alcohol dependence; Area; Attention; Base Ratios; Candidate Disease Gene; Cessation of life; Child Abuse; Cocaine Dependence; Complement; Complex; DRD2 gene; Data Set; Dependence; Detection; Discipline; Disease; Dose; Drug Addiction; Environment; Epidemiologist; Epidemiology; Etiology; Family Study; Fostering; Foundations; Functional disorder; GABA Receptor; Genes; Genetic; Goals; Investigation; Lead; Learning; Logistic Regressions; Malignant Neoplasms; Mentored Research Scientist Development Award; Mentors; Methods; Morbidity - disease rate; Neurons; Nicotine Dependence; Nicotinic Receptors; Phenotype; Play; Preparation; Prevention; Process; Research; Research Personnel; Research Scientist Award; Research Training; Role; Sampling; Smoking Behavior; Solid; Staging; Therapeutic; Tobacco; Tobacco use; Training; Trees; Work; addiction; base; career development; case control; cigarette smoking; clinical Diagnosis; design; experience; follow-up; gene environment interaction; genetic variant; genetics of alcoholism; genome wide association study; global health; improved; innovation; insight; mortality; novel; novel strategies; premature; programs; psychogenetics; public health relevance; research and development; simulation; skills; trait; treatment strategy

DESCRIPTION (provided by applicant): This proposal for a Mentored Research Scientist Award is designed to provide the candidate with the necessary training and enhanced research experience to transition into an independent drug dependence genetic statistician/genetic epidemiologist. The proposed training, in the areas of drug dependence epidemiology, psychiatric genetics, and kernel-based statistical interaction analysis will complement the candidate's previous training and existing skills, and provide a solid foundation for the candidate to become an independent investigator. This training will be advised by a multi-discipline mentoring team with extensive experience and complementary skills. The Primary Mentor, Dr. Jim Anthony, and Co-Mentor, Dr. Naomi Breslau, will advise the candidate's training in drug dependence epidemiology, with guided learning experiences via consultants on pathophysiology, etiology, clinical diagnosis, and therapeutics. Co-Mentor, Dr. Karen Friderici, and Collaborator, Dr. Laura Bierut, will supervise the candidate's training in psychiatric genetics Co-Mentor, Daniel Schaid, will advise the candidate's training in kernel-based statistical interaction analysis. The long term goal is to identify gene-gene/gene-environment (G-G/G-E) interactions that account for tobacco/nicotine dependence and related phenotypes (NDRP), and then to evaluate their role in NDRP prediction and prevention, and in personalized treatment. The research proposed in this application is to improve the detection of NDRP-related G-G/G-E interactions by employing innovative statistical genetic approaches. In the proposed research, non-parametric kernel-based statistical genetic approaches will be developed and applied to NDRP-associated genes (e.g., nAChRs sub-unit genes) and environmental determinants (e.g., childhood abuse) for (a) detecting high-order interactions, (b) discovering interactions among low-marginal-effect genetic and environmental determinants, and (c) identifying common and unique interactions accounting for NDRP and alcohol dependence and related phenotypes. An existing case-control genome-wide association study dataset from the Study of Addiction: Genetics and Environment will be used for the proposed G-G/G-E interaction analysis. The novel G-G/G-E interaction findings will likely provide new insights into the underlying NDRP pathophysiological and etiological processes, as well as have significant implications for better NDRP prediction and prevention/treatment strategies. The training and research experience gained from the proposed study will serve as the groundwork for an independent research program, including a new R01 proposal to be submitted during the second year of the K01 award interval, in order to strengthen and refine current methods for NDRP-related G-G/G-E interaction research.

描述（由申请人提供）：这项指导研究科学家奖的建议旨在为候选人提供必要的培训和增强的研究经验，以过渡到独立的药物依赖遗传学家/遗传流行病学家。在药物依赖流行病学，精神遗传学和基于内核的统计互动分析方面的拟议培训将补充候选人以前的培训和现有技能，并为候选人提供稳固的基础 成为独立研究者。一支具有丰富经验和补充技能的多学科指导团队将为这项培训提供建议。主要导师吉姆·安东尼（Jim Anthony）博士和同事纳奥米·布雷斯劳（Naomi Breslau）博士将建议候选人在药物依赖流行病学方面的培训，并通过顾问进行了有关病理生理学，病因学，临床诊断和治疗学的顾问的指导学习经验。院长Karen Friderici博士和合作者Laura Bierut博士将监督候选人在精神遗传学方面的培训Daniel Schaid，建议候选人在基于内核的统计互动分析中的候选人培训。长期目标是确定基因/基因环境（G-G/G-E）相互作用，这些相互作用解释了烟草/尼古丁依赖性和相关表型（NDRP），然后评估其在NDRP预测和预防中的作用，以及在个性化治疗中的作用。本应用中提出的研究是通过采用创新的统计遗传方法来改善与NDRP相关的G-G/G-E相互作用的检测。在拟议的研究中，将开发基于非参数的统计遗传学方法，并应用于NDRP相关基因（例如NACHRS子单位基因）和环境决定因素（例如儿童滥用）（例如，儿童滥用）（例如，（a）检测高阶相互作用，（a）发现高阶相互作用，（b）识别常见的统一和环境属性，以及环境概况，（b）的概述（b）考虑到NDRP和酒精依赖性以及相关表型。现有的病例对照基因组的关联研究数据集来自成瘾研究：遗传学和环境将用于拟议的G-G/G-E相互作用分析。新型的G-G/G-E相互作用发现可能会为基本的NDRP病理生理和病因过程提供新的见解，并对更好的NDRP预测和预防/治疗策略具有重要意义。从提议的研究中获得的培训和研究经验将作为独立研究计划的基础，包括在K01奖励间隔的第二年提交的新R01提案，以加强和完善与NDRP相关的G-G/G-E-E相互作用研究的当前方法。