GENE-ENVIRONMENT INTERPLAY IN ALCOHOLISM

描述(由申请人提供)：此K05竞争续签申请寻求对申请人的研究和初级教师指导计划的持续支持，该计划调查酒精使用障碍的发病、病程和后果中的基因-环境相互作用，特别强调了解女性AUD。自1988年以来，这位候选人一直被NIAAA资助为R01 PI，并发表了500多篇论文，其中许多被高度引用。他领导了许多关于酒精使用障碍的遗传流行病学的研究。他的职业发展计划寻求获得知识，以进一步扩大他的研究范围，利用全基因组测序(使用他的澳大利亚双胞胎家族系列进行基因发现)、元基因组学(包括其生物标记物开发的潜力)、空间流行病学(允许将与邻里酒精相关的风险因素的生态数据与现有的队列研究合并)和神经成像(使他在人类连接组项目中的作用对酒精研究界的价值最大化)中出现的机会：换句话说，寻求继续改善对遗传(可能包括元基因组)风险的表征、环境风险的表征和表型，以进一步了解基因-环境相互作用，利用独特的制度环境进行这些领域的研究。他将指导3-5名初级教员，研究重点是AUD风险的不同方面：例如：(I)严重酗酒女性缓解的预测因素；(Ii)儿童期性虐待对酒精使用模式的影响；(Iii)统计建模以检测 过量饮酒对人类大脑功能连通性的影响；(Iv)母亲酗酒、父母分离和早发性饮酒；(V)酗酒-暴食共病的潜在过程。他的研究计划集中在两个优先领域-扩展他对MOAFTS双胞胎队列的随访，专注于酒精问题缓解的预测因素；以及高风险研究，使用从现在和以前的过度饮酒者和体重指数匹配的对照组收集的粪便样本，结合细菌16S rRNA基因测序，以确定长期饮酒对肠道微生物生态的影响是否可以导致检测过度饮酒的新方法。

DESCRIPTION (provided by applicant): This K05 competing renewal application seeks continued support for the applicant's research and junior faculty mentoring program, which investigates gene-environment interplay in alcohol use disorder onset, course and consequences, with a particular emphasis on understanding female AUD. The candidate has been continuously funded by NIAAA as R01 PI since 1988, and has over 500 publications, many highly cited. He has led many investigations on the genetic epidemiology of alcohol use disorder. His career development plan seeks to acquire knowledge to further expand the reach of his research, to take advantage of emerging opportunities in whole genome sequencing (for gene discovery using his Australian twin-family series), metagenomics (including its potential for biomarker development), spatial epidemiology (to allow merging of ecological data on neighborhood alcohol-related risk-factors with existing cohort studies), and neuroimaging (to maximize the value for the alcohol research community of his role in the Human Connectome Project): in other words, seeks to continue to improve characterization of genetic (perhaps including metagenomic) risks, characterization of environmental risks, and phenotyping, to further gene-environment interplay understanding, taking advantage of the unique institutional environment for these areas of research. He will mentor 3-5 junior faculty with research focused on varied aspects of AUD risk: e.g. (i) predictors of remission in women with severe alcoholism; (ii) childhood sexual abuse effects on alcohol use patterning; (iii) statistical modeling to detect excessive drinking effects on human brain functional connectivity; (iv) maternal alcoholism, parental separation, and early-onset drinking; (v) processes underlying alcoholism-binge eating comorbidity. His research plan focuses on two priority areas - extension of his follow-up of the MOAFTS twin cohort, to focus on predictors of remission of alcohol problems; and high-risk research using fecal sample collection from current and former excessive drinkers and BMI-matched controls, combined with bacterial 16S rRNA gene sequencing, to determine whether chronic alcohol effects on gut microbial ecology can lead to new approaches for the detection of excessive drinking.