Genetics, Romantic Relationships, and Alcohol Misuse in Emerging Adulthood

成年初期的遗传学、浪漫关系和酒精滥用

• 批准号: 9095004
• 负责人: JESSICA E SALVATORE
• 金额: $ 16.45万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-05 至 2021-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9095004
• 关键词: Adolescence; Adolescent; Adopted; Adult; Age; Alcohol Phenotype; Alcohol consumption; Alcohol dependence; Alcohol or Other Drugs use; Alcohols; Area; Award; Behavior; Behavioral Genetics; Bioinformatics; Biometry; Candidate Disease Gene; Characteristics; Clinical; Collaborations; Complement; Complex; Development; Diagnosis; Educational workshop; Environment; Environmental Risk Factor; Equation; Exposure to; Fill-It; Foundations; Funding; Genes; Genetic; Genetic Predisposition to Disease; Genetic Risk; Genetic screening method; Genomics; Goals; Health Care Costs; Individual; Intervention; Laboratories; Literature; Longitudinal Studies; Mediating; Mentored Research Scientist Development Award; Mentors; Mentorship; Methods; Mission; Modeling; Molecular Genetics; National Institute on Alcohol Abuse and Alcoholism; Outcome; Pathway interactions; Pattern; Play; Process; Property; Public Health; Qualifying; Reading; Research; Research Personnel; Research Project Grants; Research Training; Resources; Risk; Rotation; Sampling; Science; Sequence Analysis; Series; Sex Characteristics; Sex Functioning; Shapes; Single Nucleotide Polymorphism; Solid; Statistical Methods; Structure; Testing; Time; Training; Training Programs; Universities; Videotape; Virginia; Wages; Work; Writing; alcohol behavior; alcohol misuse; alcohol research; alcohol use disorder; antisocial behavior; career; career development; cohort; college; deviant; drinking; emerging adult; emerging adulthood; experience; gene environment interaction; genome wide association study; high risk; high risk drinking; innovation; insight; interest; next generation sequencing; novel; peer; personalized intervention; phenotypic data; programs; prospective; public health relevance; sex; symposium

 DESCRIPTION (provided by applicant): The purpose of the proposed K01 Mentored Research Scientist Development Award is to provide the candidate with research training experiences needed to support her career goal of becoming an alcohol investigator who aims to understand the interplay between genetic factors and close relationship factors in the onset, persistence, and discontinuity of alcohol misuse (i.e., risky drinking and alcohol use disorder). To expand her research career and support this career goal, the candidate's training goals under this award are to: (1) establish an integrated understanding of alcohol misuse in emerging adulthood that formally ties together her research interests in alcohol outcomes, romantic relationships, and behavior genetics; and (2) develop a solid foundation in the use and interpretation of advanced genetic (e.g., next generation sequencing), genomic (e.g., functional annotation), and statistical (e.g., structural equation modeling) methods needed to carry out an independent interdisciplinary program of research on gene-environment interplay in the development of alcohol misuse. These goals will be achieved through a structured series of mentored research experiences, a molecular genetics laboratory rotation, coursework/workshops in bioinformatics and statistical genetics, directed readings with mentors and collaborators who are experts in their respective fields, and exposure to clinical interventions for hazardous/harmful drinking. The candidate will also participate in additional activities to further support her career development including training in the responsible conduct of research, grant writing, and presenting research at professional conferences. The candidate will complete this training at Virginia Commonwealth University (VCU) under the primary mentorship of Dr. Danielle Dick (expertise in gene-environment interplay for alcohol use disorder), with co-mentorship provided by Dr. Thomas Dishion (expertise in pathways toward adolescent and adult substance use, with an emphasis on interpersonal factors), Dr. Mikhail Dozmorov (expertise in bioinformatics and biostatistics), and Dr. Shaunna Clark (expertise in structural equation modeling). Alcohol and behavior genetics are active areas of research at VCU, and thus the candidate has unparalleled support and resources to further her research career. The scientific objective of this proposal is to examine how alcohol dependence genetic predispositions influence pathways to emerging adulthood (ages 18-29) relationship quality and partner selection, and how characteristics of one's relationship and partner further shape trajectories of alcohol misuse. The central hypothesis is that gene-environment correlation (rGE) and gene-environment interaction (G x E) processes contribute to these pathways and trajectories. The candidate's approach leverages novel training in bioinformatics to characterize aggregate genetic risk for alcohol dependence by creating biologically refined polygenic scores. The candidate will then use biologically refined polygenic scores to test gene-environment interplay hypotheses in two NIAAA-funded genetically informative prospective longitudinal studies of emerging adults: Spit for Science (PIs: Dick and Kendler) and the Project Alliance 1 (PAL-1) Relationship Study (PI: Dishion). Spit for Science is a sample of four cohorts of college freshmen (n~10,000) who are followed annually (ages ~18-23). The PAL-1 Relationship Study is a sample of ~400 romantic dyads (ages ~28-29). One partner in each dyad has been studied since adolescence, and a videotaped couple's assessment and dyadic longitudinal phenotypic data are collected as part of the relationship study. These studies complement one another in that Spit for Science allows the candidate to examine how the hypothesized gene-environment interplay effects unfold across a six-year period covering the beginning of emerging adulthood, and PAL-1 will provide insights into how the hypothesized effects play out in a specific dyadic relationship in the latter part of emerging adulthood. The three aims of this work are to: (1) Examine whether alcohol dependence genetic predispositions are associated with the quality of one's relationship or the alcohol misuse of one's romantic partner (i.e., rGE), and whether these associations are mediated by antisocial behavior and affiliations with deviant peers in adolescence; (2) Examine whether the quality of one's relationship or the alcohol misuse of one's romantic partner moderate alcohol dependence genetic predispositions to predict alcohol misuse (i.e., G x E); (3) Examine whether the patterns observed in Aims 1 and 2 differ by sex. This research is significant because it fills a critical need for studies of gene-environment interplay for alcohol misuse and romantic relationship factors in emerging adulthood, which is the period of highest risk for the development of alcohol use disorder. Furthermore, the candidate's proposal to integrate alcohol dependence genome-wide association study results and functional annotation information to develop biologically refined polygenic scores is an innovative departure from the candidate gene approach typically adopted in studies of gene-environment interplay in alcohol research. In summary, the proposed award will provide the candidate with new research and training experiences needed to launch an independent, innovative research program on genetics, romantic relationships, and alcohol misuse that is relevant to NIAAA's mission to identify how genetic and salient environmental risk and protective factors for alcohol misuse interface across development.

 描述（由申请人提供）：拟议的 K01 指导研究科学家发展奖的目的是为候选人提供所需的研究培训经验，以支持她成为酒精调查员的职业目标，旨在了解遗传因素与密切关系之间的相互作用酒精滥用（即危险饮酒和酒精使用障碍）的发生、持续和中断的因素。为了扩大她的研究生涯并支持这一职业目标，该奖项下候选人的培训目标是： (1) 建立对成年初期滥用酒精的综合理解，将她在酒精后果、浪漫关系和行为遗传学方面的研究兴趣正式联系起来；(2) 在先进遗传学的使用和解释方面打下坚实的基础（例如，下一代测序）、基因组（例如功能注释）和统计（例如结构方程建模）方法需要开展关于酒精滥用发展中基因与环境相互作用的独立跨学科研究计划，这些目标将得以实现。通过结构化的系列候选人还将参加指导研究经验、分子遗传学实验室轮换、生物信息学和统计遗传学课程/研讨会、与各自领域专家的导师和合作者进行定向阅读，以及接触危险/有害饮酒的临床干预措施。进一步支持她的职业发展的其他活动，包括负责任的研究行为、资助写作和在专业会议上展示研究的培训。候选人将在丹妮尔·迪克博士的主要指导下在弗吉尼亚联邦大学 (VCU) 完成这项培训。 （酒精使用障碍的基因与环境相互作用方面的专业知识），由 Thomas Dishion 博士（青少年和成人物质使用途径方面的专业知识，重点是人际因素）、Mikhail Dozmorov 博士（生物信息学方面的专业知识）提供共同指导和生物统计学），以及 Shaunna Clark 博士（结构方程模型方面的专业知识）。酒精和行为遗传学是弗吉尼亚联邦大学的活跃研究领域，因此候选人得到了无与伦比的支持。该提案的科学目标是研究酒精依赖遗传倾向如何影响成年期（18-29 岁）的关系质量和伴侣选择，以及一个人的关系和伴侣的特征如何进一步塑造轨迹。核心假设是基因-环境相关性 (rGE) 和基因-环境相互作用 (G x E) 过程有助于这些途径和轨迹。候选人的方法利用生物信息学的新颖训练来表征总体。然后，候选人将使用生物学精炼的多基因评分来测试两项由 NIAAA 资助的针对新兴成年人的遗传信息前瞻性纵向研究中的基因-环境相互作用假设：Spit for Genetic Sc​​ience（PI：Dick 和Kendler）和项目联盟 1 (PAL-1) 关系研究（PI：Dishion）是每年跟踪的四组大学新生（n~10,000）的样本。 （年龄 ~18-23 岁）。 ​​PAL-1 关系研究是约 400 个浪漫二人组（年龄约 28-29 岁）的样本，从青春期开始就对每个二人组中的一个伴侣进行了研究，并录制了一对情侣的评估和二人关系。纵向表型数据是作为关系研究的一部分收集的，这些研究相互补充，因为 Spit for Science 允许候选人检查在六年期间内基因与环境相互作用的影响如何展开。 PAL-1 将提供有关在成年初期的特定二元关系中培养效应如何发挥作用的见解。这项工作的三个目的是：（1）检查酒精依赖是否遗传。倾向与一个人的关系质量或一个人的浪漫伴侣的酗酒（即，rGE）有关，以及这些关联是否是由青春期的反社会行为和与异常同龄人的关系所介导的（2）；检查一个人的关系质量或一个人的浪漫伴侣的酒精滥用是否会调节酒精依赖遗传倾向，以预测酒精滥用（即 G x E）；（3）检查目标 1 和 2 中观察到的模式是否因性别而异。这项研究意义重大，因为它满足了研究成年初期酒精滥用和浪漫关系因素的基因与环境相互作用的迫切需要，这是发生酒精使用障碍的最高风险时期。此外，候选人的提案整合酒精依赖全基因组关联研究结果和功能注释信息来开发生物学精炼的多基因评分，是对酒精研究中基因与环境相互作用研究中通常采用的候选基因方法的创新。 总之，拟议的奖项将提供。具有新的研究和培训经验的候选人需要启动一项关于遗传学、恋爱关系和酒精滥用的独立、创新的研究项目，该项目与 NIAAA 的使命相关，即确定遗传和显着的环境风险以及酒精滥用的保护因素如何在整个发展过程中相互作用。