Gene-Environment Interplay in Alcoholism

描述（由申请人提供）：本K 05申请要求5年的支持，以使PI能够将受保护的时间和精力投入到其研究和指导计划中，重点关注酗酒的基因-环境相互作用和风险机制，使其免受行政责任的侵害。Pi的指导将吸引4名初级教师作为NIAAA资助的R 01调查员，在以下实质性领域追求独立性：（i）与父母酗酒相关的后代环境风险和社会情绪问题，以及幼儿和学龄前儿童的并发症，（ii）非常早发性酒精和其他物质使用的病因学，特别关注与父母离婚/未婚有关的风险机制，（iii）从青春期到青年期的酒精使用和问题的过渡，特别是童年攻击性创伤的影响，以及（iv）个人和后代的结果，和风险因素，与缓解与恢复酒精问题的妇女与反复酒后驾车。这些不同的研究领域是很好的匹配与圆周率的长期利益（一）酗酒的妇女，和（ii）的环境背景下，酗酒风险的遗传传递发生。此外，PI将通过R 01支持的项目继续为酗酒领域做出贡献，这些项目包括：（i）MOAFTS的30岁随访，MOAFTS是一对女性同性双胞胎的出生队列，从中位年龄15岁开始随访，以确定遗传影响对酒精问题的发生和恢复与持续性的介导者和调节者;（ii）对澳大利亚双胞胎子女队列的持续随访，对比与母亲或父亲酗酒相关的结果（高环境风险，高遗传风险）与仅在父母的MZ双胞胎中酗酒（降低的环境风险，高遗传风险），或DZ双胞胎（中等遗传风险）和控制;以及（iii）利用协调评估的方法学贡献和二次数据分析，以及有关环境和基因环境相互作用机制的信息量，澳大利亚双胞胎登记处和MOAFTS的研究（包括4000人ATR全基因组关联数据的可用性）。了解酗酒遗传的环境背景应该提高对如何识别和干预高风险群体问题和基因发现的理解。

DESCRIPTION (provided by applicant): 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.