Gene-Environment Interplay in Alcoholism

描述（由申请人提供）：这份K05申请要求5年的支持，以允许PI将受保护的时间和精力投入到他的研究和指导计划中，重点研究酗酒的基因-环境相互作用和风险机制，使他免于行政责任的侵犯。Pi的指导将聘请4名年轻教师作为niaaa资助的R01调查员，在以下实质性领域追求独立：(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）非常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/未婚相关的风险机制。（三）从青春期到青年时期酒精使用的转变和问题，特别是儿童期攻击性创伤的影响，以及（四）与反复酒后驾车妇女酒精问题缓解与恢复相关的个人和后代后果以及风险因素。这些不同的研究领域与Pi的长期兴趣(i)女性酗酒，以及（ii）酗酒风险遗传传播发生的环境背景相匹配。此外，PI将通过r01支持的项目继续对酒精中毒领域作出贡献，这些项目包括(i)对MOAFTS进行30岁时的随访，这是一组从中位年龄15岁开始跟踪的同性女性双胞胎出生队列，以确定基因对酒精问题开始和恢复与持续的影响的调节因子和调节因子；（ii）对澳大利亚双胞胎儿童队列进行持续随访，对比与母亲或父亲酗酒（高环境风险，高遗传风险）相关的结果与仅在父母的MZ同卵双胞胎（低环境风险，高遗传风险）或DZ同卵双胞胎（中等遗传风险）和对照中酗酒相关的结果；（iii）利用澳大利亚双登记和MOAFTS研究的协调评估以及环境和基因环境相互作用机制的信息（包括4000个个体的ATR全基因组关联数据的可用性）的方法贡献和次要数据分析。了解酒精中毒基因遗传的环境背景可以提高对如何识别和干预问题高危人群以及基因发现的理解。

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.