Gene-Environment Interplay in Alcoholism

酗酒中基因与环境的相互作用

基本信息

批准号：
8321077
负责人：
ANDREW C. HEATH
金额：
$ 18.45万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-05 至 2013-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8321077
关键词：
21 year old Address Adolescence Adult Age Age Distribution Age Reporting Alcohol abuse Alcohol consumption Alcohol dependence Alcohol or Other Drugs use Alcoholism Alcohols Antisocial Personality Disorder Anxiety Disorders Area Attention Attention deficit hyperactivity disorder Australia Bayesian Method Behavior Birth Blood Blood specimen Budgets Candidate Disease Gene Child Childhood Chromosome Mapping Cohort Studies Collection Commit Comorbidity Complex DNA Data Data Analyses Data Set Dependence Development Diagnosis Diagnostic Disease Disease remission Divorce Drug Addiction Drug usage Drunk driving Early-life trauma Eating Disorders Ensure Environment Environmental Exposure Environmental Risk Factor Epidemiologic Methods Equation Ethnic Origin Etiology Event Factor Analysis Faculty Familiarity Family Fathers Female Frequencies Funding Gender Generations Genes Genetic Genetic Research Genetic Risk Genotype Goals Growth Heavy Drinking Heritability Illicit Drugs Individual Interest Group Interview Intoxication Journals Knowledge Laws Lead Life Literature Longevity Major Depressive Disorder Marital Status Markov Chains Marriage Measures Mediator of activation protein Medical Mental Depression Mentors Methods Missouri Modeling Molecular Epidemiology Mothers National Institute on Alcohol Abuse and Alcoholism Neighborhoods Nursery Schools Obesity Occupational Outcome Panic Disorder Parenting behavior Parents Patient Self-Report Pattern Perception Pharmaceutical Preparations Post-Traumatic Stress Disorders Probability Psychopathology Recording of previous events Recovery Recurrence Reporting Reproduction Request for Applications Research Research Personnel Research Project Grants Residual state Resolution Risk Risk Factors Role Saliva Sample Size Sampling Schools Screening procedure Secondary to Siblings Social Phobia Staging Statistical Methods Substance Use Disorder Surveys Symptoms TNFRSF5 gene Telephone Telephone Interviews Testing Time Tobacco Toddler Trauma Twin Multiple Birth Update Variant Weight Woman Work Workplace age effect alcohol use disorder base cohort college comparison group cost design deviant divorce/separation drinking early adolescence early onset emerging adulthood environmental change follow-up gene discovery genetic association genetic epidemiology genetic variant genetics of alcoholism genome wide association study genome-wide high risk human subject improved informant interest next generation offspring parental alcoholism pediatric trauma peer problem drinker programs prospective sex simulation skills stressor trait transmission process trend young adult young woman

项目摘要

This K05 application requests 5 years of support to allow the PI to commit protected time and effort to his research and mentoring program focused on gene-environment interplay and risk-mechanisms in alcoholism, freeing him from the encroachment of administrative responsibilities. The Pi's mentoring will engage 4 junior faculty in the pursuit of independence as NIAAA-funded R01 investigators, in the substantive areas of (i) offspring environmental risks and socioemotional problems associated with parental alcoholism, and comorbidity during the toddler and preschool years, (ii) etiology of very early-onset alcohol and other substance use, with a particular focus on risk-mechanisms associated with parental divorce/never marriage, (iii) transitions in alcohol use and problems from adolescence through young adulthood, particularly the impact of childhood assaultive trauma, and (iv) personal and offspring outcomes, and risk-factors, associated with remission versus recovery of alcohol problems in women with recurrent drunk driving. These diverse research areas are well-matched with the Pi's long-standing interests in (i) alcoholism in women, and (ii) the environmental contexts in which the genetic transmission of alcoholism risk occurs. Additionally, the PI will continue his contributions to the alcoholism field through R01-supported projects which involve (i) follow-up at age 30 of MOAFTS, a birth cohort of female like-sex twin pairs followed from median age 15 to identify mediators and moderators of genetic influences on onset of and recovery from versus persistence in alcohol problems; (ii) continued follow-up of the Australian Children-of-Twins cohorts, contrasting outcomes associated with maternal or paternal alcoholism (high environmental risk, high genetic risk) versus alcoholism only in parent's MZ co-twin (reduced environmental risk, high genetic risk), or DZ co-twin (intermediate genetic risk) and controls; and (iii) methodologic contributions and secondary data-analyses that take advantage of the coordinated assessments, and informativeness about environmental and gene environmental interplay mechanisms, of studies in the Australian twin register and MOAFTS (including the availability of ATR genome-wide association data on 4000 individuals). Understanding environmental contexts for the genetic inheritance of alcoholism should improve both understanding of how to identify and intervene with groups at high-risk for problems, and gene-discovery.

该 K05 申请要求 5 年的支持，以便 PI 能够将受保护的时间和精力投入到他的研究和指导项目中，该项目专注于酗酒中的基因-环境相互作用和风险机制，使他免受行政责任的侵扰。 Pi 的指导将吸引 4 名初级教师作为 NIAAA 资助的 R01 调查员寻求独立，其研究领域包括 (i) 与父母酗酒相关的后代环境风险和社会情感问题，以及幼儿和学龄前时期的共病，(ii) ) 极早发病的酒精和其他物质使用的病因学，特别关注与父母离婚/不结婚相关的风险机制，(iii)酒精使用和从青春期到成年早期的问题，特别是儿童期攻击性创伤的影响，以及（iv）个人和后代的结果以及与经常醉酒驾驶的女性酒精问题的缓解与恢复相关的风险因素。这些不同的研究领域与 Pi 长期以来对 (i) 女性酗酒问题和 (ii) 酗酒风险遗传传播的环境背景的兴趣非常吻合。此外，PI 将通过 R01 支持的项目继续为酗酒领域做出贡献，其中包括 (i) MOAFTS 30 岁时的随访，这是一个从中位年龄 15 岁开始跟踪的女性同性双胞胎出生队列，以确定调解者和遗传对酒精问题的发作和恢复与持续性影响的调节因素； (ii) 对澳大利亚双胞胎儿童队列进行持续随访，对比母亲或父亲酗酒（高环境风险、高遗传风险）与仅父母同卵双胞胎酗酒（环境风险降低、高遗传风险）相关的结果风险），或 DZ 双胞胎（中等遗传风险）和控制； (iii) 方法学贡献和二次数据分析，利用澳大利亚双胞胎登记册和 MOAFTS 的研究的协调评估以及有关环境和基因环境相互作用机制的信息（包括 ATR 全基因组关联数据的可用性） 4000 人）。了解酗酒遗传的环境背景应该可以提高对如何识别和干预问题高风险群体的理解，以及基因发现。