Project 5. Molecular Epidemiology of Alcoholism and Comorbid Disorders

酒精中毒及其共病的分子流行病学研究 这个MARC研究项目，项目5，寻求建立在基因发现项目的基础上，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附属酒精-QTL IRPG联盟(Pis Heath，Martin，Madden，Todd)，正在研究社区确定的酗酒者 以及重度吸烟者和他们的成年亲属，通过将分子遗传成分整合到5 前瞻性纵向研究(Pis Anokhin，Bucholz，Chassin，Heath，Sher：ABCHS队列) 年龄--从青春期早期到成年早期。除了在网上完成DNA收集之外 Heath队列(1-2岁)，该研究项目将对有限数量的候选人进行基因分型 基因(1-2岁)；DNA阵列遗传关联分析(3-5岁)。我们专注于有限数量的 预期数据将有助于了解病因学的候选表型 酗酒。第一候选表型和候选基因的选择是以MARC为指导的 关注行为受控、负面情绪调节和控制的重叠机制的作用 酒精使用障碍(AUD)病因学中的药物脆弱性，强调AUD表型 与(A)外化症状、(B)耐受性和量化消费指数、(C)同时发生有关 与烟草依赖有关，以及(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.