Gene-Environment Interplay in Alcoholism

描述（由申请人提供）：此 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，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，以及幼儿和学龄前儿童的合并症，(ii) 极早发作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，MOAFTS 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，以确定遗传影响酒精问题发病和恢复与持续存在的中介因素和调节因素； (ii) 继续对澳大利亚双胞胎儿童队列进行随访，将与母亲或父亲酗酒（高环境风险、高遗传风险）相关的结果与仅父母的同卵双胞胎（环境风险降低、高遗传风险）或同卵双胞胎（中度遗传风险）和对照的酗酒结果进行对比； (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 4000 名个体的 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。

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.