Project 5. Molecular Epidemiology of Alcoholism and Comorbid Disorders

酒精中毒与共病的分子流行病学 这个MARC研究项目，项目5，旨在建立在基因发现项目，如COGA （酒精中毒遗传学合作研究：PI，Porjesz）和类似项目（例如Pis Hill，Kendler） 他们正在研究治疗确定的酗酒者及其亲属，以及MARC附属的酒精QTL。 IRPG财团（Pis Heath，Martin，Madden，托德），该财团正在研究社区确定的酗酒者 和重度吸烟者及其成年亲属，通过将分子遗传成分纳入5 前瞻性纵向研究（Pis Anokhin、Bucholz、Chassin、Heath、Sher：ABCHS队列），涵盖 年龄范围从青春期早期到青年期。除了完成DNA采集外， 健康队列（1-2年），本研究项目将对有限数量的候选人进行基因分型 基因（1-2年）和DNA阵列遗传关联分析（3-5年）。我们专注于有限数量的 候选表型，预期前瞻性数据可为了解病因提供信息 酒精中毒第一候选表型和候选基因的选择由MARC指导 关注行为控制不足、负面情绪调节和 酒精使用障碍（AUD）病因学的药理学脆弱性，强调AUD表型 与（a）外化症状，（B）耐受性和定量消耗指数，（c）共现 烟草依赖;（d）负面影响。第二组候选基因将是 选自COGA、澳大利亚IRPG和 其他研究。

MOLECULAR EPIDEMIOLOGY OF ALCOHOLISM AND COMORBID DISORDERS This MARC research project, project 5, seeks to build upon gene-discovery projects such as COGA (Collaborative Study on the Genetics of Alcoholism: PI, Porjesz) and similar projects (e.g. Pis Hill, Kendler) which are studying treatment-ascertained alcoholics and their relatives, and the MARC-affiliated Alcohol-QTL IRPG consortium (Pis Heath, Martin, Madden, Todd), which is studying community-ascertained alcoholics and heavy smokers and their adult relatives, by incorporating a molecular genetic component into 5 prospective longitudinal studies (Pis Anokhin, Bucholz, Chassin, Heath, Sher: ABCHS Cohorts) spanning the age-range from early adolescence into young adulthood. In addition to completing DNA collection on the Heath cohort (years 1-2), this research project will conduct genotyping for a limited number of candidate genes (years 1-2); and DNA array genetic association analysis (years 3-5). We focus on a limited number of candidate phenotypes where prospective data are expected to be informative for understanding the etiology of alcoholism. The selection of the first candidate phenotypes and candidate genes is guided by the MARC focus on the roles of overlapping mechanisms of behavioral under-control, negative affect regulation and pharmacologic vulnerability in the etiology of alcohol use disorders (AUDs), emphasizing AUD phenotypes associated with (a) externalizing symptoms, (b) tolerance and quantitative consumption indices, (c) cooccurrence with tobacco dependence, and (d) negative affect. The second set of candidate genes will be selected from replicated genome-wide association (GWA) study results from COGA, Australian IRPG and other studies.