Genetic Contributions to Smoking and Internalizing Problems in Adolescence

描述(由申请人提供)：这一职业发展奖(K01)将为候选人提供必要的技能，以开发一个独立的研究计划，专注于将遗传方法与候选人已经很强的纵向建模技能相结合，以探索和澄清青少年时期吸烟和内化问题之间相互作用的病因。尽管在过去的二十年里，青春期的吸烟率有所下降，但青春期仍然是吸烟开始和内化问题增加的最大风险的发育期。在这个脆弱的时期，要弄清香烟使用和内化问题共同发生的复杂病因，需要使用多种方法。目前提案的总体目标是测试日益复杂的纵向模型，这些模型探索青少年吸烟和内化问题之间的共同发生在多大程度上受到遗传和环境因素的影响，并包括测量到的遗传变异。培训计划将在弗吉尼亚联邦大学弗吉尼亚精神病学和行为遗传学研究所完成，旨在为候选人提供遗传流行病学、数量遗传学和分子遗传学方面的技能。候选人将获得以下知识和技能：a)进行单变量、双变量和多变量遗传信息研究，以确定吸烟开始、进展和重度吸烟、尼古丁依赖和内化问题的遗传和环境风险因素；b)进行纵向基因信息研究，通过探索遗传和环境因素解释行为之间的协变程度，阐明吸烟和内化问题所涉及的因果路径；以及c)对青少年双胞胎进行遗传信息生态瞬时评估研究，以探索这些问题行为之间的因果路径。这些技能将通过正式的课程作业、有指导的研究项目和教学培训相结合来发展。拟议的研究计划结合了对现有的青春期双胞胎纵向研究的分析和一个原始数据收集试点项目。现有的关于青少年双胞胎的纵向研究包括瑞典双胞胎儿童和青少年发育研究、明尼苏达州双胞胎和家庭研究、弗吉尼亚双胞胎青少年行为发育研究、国家青少年健康纵向研究、GEDI(NIDA遗传学联合会的基因、环境、发育倡议部分)。在试点项目中，候选人将收集16岁和17岁青少年双胞胎的瞬时吸烟和情绪数据，这些数据是从基于人口的双胞胎登记中招募的，该登记由50,000多名双胞胎组成。培训活动和结果将用于 制定R01提案，对14至17岁的青少年双胞胎进行前瞻性瞬时评估和基因分型研究。

DESCRIPTION (provided by applicant): This Career Development Award (K01) will provide the candidate with the necessary skills to develop an independent research program focused on integrating genetic methodologies to the candidate's already strong longitudinal modeling skills to explore and clarify the etiology of the interplay between cigarette use and internalizing problems during adolescence. Despite decreases in prevalence of smoking during adolescence in the past two decades, adolescence continues to be the developmental period of greatest risk for cigarette use onset and increase in internalizing problems. Clarifying the complex etiological pathways involved in the co-occurrence between cigarette use and internalizing problems during this vulnerable time requires using multiple methodologies. The overall aim of the current proposal is to test increasingly complex longitudinal models that explore the degree to which the co-occurrence between adolescent cigarette use and internalizing problems are influenced by genetic and environmental factors and to include measured genetic variants. The training plan will be completed at the Virginia Institute for Psychiatric and Behavioral Genetics at Virginia Commonwealth University and is designed to provide the candidate with skills in genetic epidemiology, quantitative genetics, and molecular genetics. The candidate will acquire the knowledge and skills to a) conduct univariate, bivariate, and multivariate genetically informed studies to identify the genetic and environmental risk factors in smoking initiation, progression t heavier smoking, nicotine dependence, and internalizing problems; b) conduct longitudinal genetically informed studies to clarify the causal pathways involved in cigarette use and internalizing problems by exploring the degree to which genetic and environmental factors explain the covariance between the behaviors; and c) conduct genetically informed ecological momentary assessment studies of adolescent twin pairs to explore the causal pathway between these problems behaviors. These skills will be developed through a combination of formal coursework, mentored research projects, and didactic training. The proposed research program involves a combination of analysis of existing longitudinal studies of adolescent twins and an original data collection pilot project. The existing longitudinal studies of adolescent twins inclue the Swedish Twin Study of Child and Adolescent Development, the Minnesota Twin and Family Study, the Virginia Twin Study of Adolescent Behavioral Development, the National Longitudinal Study of Adolescent Health, the GEDI (Genes, Environment, Development Initiative part of NIDA's Genetics Consortium). In the pilot project, the candidate will collect momentary cigarette use and mood data of 16- and 17-year-old adolescent twin pairs recruited from a population-based twin registry comprised of over 50,000 twins. Training activities and results will be used to develop a R01 proposal for a prospective momentary assessment and genotyping study of 14 to 17 year old adolescent twins.