EXPLORING GENETIC INFLUENCES ON ALCOHOL USE USING NOVEL STATISTICAL METHODS

使用新颖的统计方法探索遗传对饮酒的影响

• 批准号: 7890564
• 负责人: Jennifer F. Buckman
• 金额: $ 12.95万
• 依托单位: RUTGERS, THE STATE UNIV OF N.J.
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-10 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7890564
• 关键词: Acute; Affect; Alcohol abuse; Alcohol consumption; Alcohol dependence; Alcohol or Other Drugs use; Alcoholism; Alcohols; Alleles; Arousal; Autonomic nervous system; Behavior; Cardiovascular system; Cells; Characteristics; Cheek structure; Chromosomes, Human, Pair 4; Cognitive; Collaborations; Consult; Cues; DNA; Data; Development; Dimensions; Dose; Drug Addiction; Drug usage; Educational workshop; Electroencephalography; Emotional; Emotional Stress; Failure; Family history of; Foundations; GABA-A Receptor; Generations; Genes; Genetic; Genetic Polymorphism; Genomics; Genotype; Goals; Haplotypes; Individual; Individual Differences; Intoxication; Link; Logic; Measures; Mentors; Methods; Molecular Genetics; Motivation; N.I.H. Research Support; Nervous System Physiology; Participant; Pathway interactions; Patient Self-Report; Personality; Persons; Pharmaceutical Preparations; Phenotype; Physiological; Physiological Processes; Preventive Intervention; Process; Psychophysiology; Psychosocial Assessment and Care; Questionnaires; Reaction Time; Regulation; Reporting; Research; Research Personnel; Research Training; Rest; Risk; Sampling; Severities; Single Nucleotide Polymorphism; Staging; Statistical Methods; Stimulus; Stress; Symptoms; Techniques; Testing; Training; Trees; Variant; addiction; alcohol related problem; alcohol response; alcohol sensitivity; alcohol use disorder; base; biological systems; career; career development; data modeling; design; drinking behavior; environmental stressor; genetic analysis; heart rate variability; indexing; neurogenetics; novel; novel strategies; parent project; psychosocial; receptor; research study; response; statistics; stem; symposium; theories; trait; treatment program; young adult

DESCRIPTION (provided by applicant): The training and research plans of this second revised K01 application will directly advance the candidate's long term career goal of developing an independent, transdisciplinary line of research that investigates subtypes of risk for alcohol-related problems and of alcohol use disorders based on phenotypic and genotypic information. Career development is sought in statistical genetics (related to hypothesis generation and testing), molecular genetics, and their integration with alcohol studies. These training objectives will be accomplished through coursework, workshops, seminars, and conferences; through extensive mentoring and consulting with senior investigators whose research is directly relevant to this application; and through development of collaborations. These activities will provide the foundation for the research plan, which combines nontraditional quantitative methods with an intermediate phenotype approach to generate conceptually- and empirically-based hypotheses about neurogenetic influences on physiological processes using highly informative yet small scale (N<500) study data. More specifically, the research plan seeks to add a genetic component to two ongoing NIH-supported projects that examine the coordinated function of multiple dynamically-interrelated biological systems and that provide in depth assessment of psychosocial and psychophysiological characteristics related to alcohol use. Genomic DNA is being collected from young adult participants who span the continuum of substance use behaviors and single nucleotide polymorphisms in GABA-A receptor subunit genes will be used as initial genotype targets. A highly sensitive index of heart rate variability - at rest, during cue exposure and acute alcohol challenge - will be used as an initial intermediate phenotype. These initial targets may identify a subset of individuals with high addiction liability due to poor modulation of emotional arousal. The overall aim is to use advanced statistics as a novel approach to identifying the multiple pathways of risk for problematic alcohol use behaviors and suggesting new, targeted approaches to treatment. Hypotheses generated from these discovery-oriented, early-stage studies will subsequently be tested with independent samples gathered through collaborations and in de novo R01 applications. This application applies cutting-edge statistical strategies to the analysis of genetic and physiological data in an effort to explore the genetic basis of drinking behaviors in a new way. This approach may be useful for identifying subtypes of risk for alcohol-related problems and suggesting ways to make prevention, intervention and treatment programs more effective.

描述（由申请人提供）：第二次修订的 K01 申请的培训和研究计划将直接推进候选人的长期职业目标，即开发独立、跨学科的研究路线，调查酒精相关问题和酒精使用的风险亚型基于表型和基因型信息的疾病。职业发展寻求统计遗传学（与假设生成和检验相关）、分子遗传学及其与酒精研究的整合。这些培训目标将通过课程、讲习班、研讨会和会议来实现；通过对研究与本申请直接相关的高级研究人员进行广泛的指导和咨询；并通过合作的发展。这些活动将为研究计划奠定基础，该计划将非传统定量方法与中间表型方法相结合，利用信息量大但规模小（N<500）的研究数据，生成基于概念和经验的关于神经遗传对生理过程影响的假设。更具体地说，该研究计划旨在将遗传成分添加到两个正在进行的 NIH 支持的项目中，这些项目检查多个动态相互关联的生物系统的协调功能，并提供与酒精使用相关的心理社会和心理生理特征的深入评估。正在从跨越物质使用行为连续体的年轻成年参与者中收集基因组 DNA，GABA-A 受体亚基基因中的单核苷酸多态性将用作初始基因型目标。心率变异性的高度敏感指数（在休息时、在提示暴露期间和急性酒精挑战期间）将被用作初始中间表型。这些初始目标可能会识别出由于情绪唤起调节不佳而具有高成瘾倾向的个体子集。总体目标是利用先进的统计数据作为一种新方法来识别有问题的饮酒行为的多种风险途径，并提出新的、有针对性的治疗方法。这些以发现为导向的早期研究产生的假设随后将通过合作和从头 R01 应用收集的独立样本进行测试。该应用程序将尖端的统计策略应用于遗传和生理数据分析，试图以新的方式探索饮酒行为的遗传基础。这种方法可能有助于识别酒精相关问题的风险亚型，并提出使预防、干预和治疗计划更有效的方法。