MARC: Genetic Epidemiology of Alcoholism & Comorbidity

MARC：酒精中毒的遗传流行病学

• 批准号: 6695960
• 负责人: ANDREW C. HEATH
• 金额: $ 136.55万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-06-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6695960
• 关键词: alcoholism /alcohol abuse; clinical research; comorbidity; family genetics; gene environment interaction; genetic susceptibility; human subject

DESCRIPTION (provided by applicant): This is the first competing continuation for the multi-site Midwest Alcoholism Research Center (MARC). The broad focus of our research is the etiology and course of alcohol problems and associated comorbidity in community (rather than clinically ascertained) samples, with an emphasis on prospective high-risk, behavioral and molecular genetic, genetic epidemiologic and experimental perspectives, and with a particular focus on adolescents and youth. The MARC is organized as: (i) an Administrative Core, under the leadership of MARC Director Heath and Scientific and Administrative Co-Directors Sher and Bucholz, which is responsible for coordinating MARC-based research projects with each other, and with our broader R01-supported Portfolio of genetic, prospective high-risk and human experimental studies, as well as for assessment, ascertainment, data-management and methodologic support for MARC-based research projects; (ii) four research studies; and (iii) a pilot to facilitate the development of new alcohol researchers, as well as new directions for established investigators. The research studies include four parts. First, investigating in the human experimental laboratory interactive effects of alcohol and tobacco on measures of sensitivity to alcohol effects (postural instability) or tobacco effects (physiologic tremor). Second, using a children-of-twins paradigm to investigate the effects of environmental consequences of maternal alcoholism, including effects that may interact with offspring genotype, by contrasting outcomes in offspring 7 years and older who are either offspring of an alcoholic mother (at high genetic risk, and high environmental risk), or of an unaffected mother who may have (a) a monozygotic twin sister who is alcoholic (also high genetic risk, but reduced environmental risk), or (b) an alcoholic dizygotic twin sister (intermediate genetic risk, reduced environmental risk), or (c) an unaffected twin sister (low genetic and low environmental risk). Third, extending 4 ongoing studies that have followed samples prospectively from adolescence into young adulthood, by adding a molecular genetic component, to investigate the developmental unfolding of candidate gene effects on risk. Fourth, seeking to bridge the gap between epidemiologic and genetic epidemiologic studies of alcohol-tobacco comorbidity, and human experimental studies, as an ecological study of the co-occurrence of alcohol and tobacco use and their motivational sequelae, assessed by electronic diary. Together these are integrated by our desire to advance etiological research on genotype x environment interaction effects on alcoholism risk at multiple levels of analysis.

描述（由申请人提供）：这是多站点中西部酗酒研究中心 (MARC) 的第一个竞争性延续。我们研究的广泛重点是社区（而不是临床确定的）样本中酒精问题和相关合并症的病因和病程，重点是前瞻性高风险、行为和分子遗传学、遗传流行病学和实验观点，并特别关注青少年。 MARC 的组织形式为：(i) 行政核心，由 MARC 主任 Heath 以及科学和行政联合主任 Sher 和 Bucholz 领导，负责相互协调基于 MARC 的研究项目，以及我们更广泛的 R01 支持的遗传、前瞻性高风险和人体实验研究组合，以及对基于 MARC 的研究的评估、确定、数据管理和方法学支持 项目； ㈡ 四项研究； (iii) 进行试点，以促进新的酒精研究人员的发展，并为现有的研究人员提供新的方向。研究内容包括四个部分。首先，在人体实验实验室中研究酒精和烟草对酒精效应（姿势不稳定）或烟草效应（生理性震颤）敏感性测量的相互作用影响。其次，使用双胞胎子女范式来研究母亲酗酒对环境后果的影响，包括可能与后代基因型相互作用的影响，通过对比 7 岁及以上的后代的结果，这些后代要么是酗酒母亲的后代（具有高遗传风险和高环境风险），要么是未受影响的母亲，她可能有（a）一个酗酒的同卵双胞胎姐妹（也有高遗传风险，但 环境风险降低），或 (b) 酗酒的异卵双胞胎姐妹（中等遗传风险，环境风险降低），或 (c) 未受影响的双胞胎姐妹（低遗传风险和低环境风险）。第三，通过添加分子遗传成分，扩展正在进行的四项研究，这些研究前瞻性地跟踪了从青春期到成年早期的样本，以研究候选基因对风险影响的发育过程。第四，寻求弥合酒精-烟草合并症的流行病学和遗传流行病学研究与人体实验研究之间的差距，作为通过电子日记评估的酒精和烟草使用同时发生及其动机后遗症的生态研究。我们希望在多个分析水平上推进基因型 x 环境相互作用对酗酒风险影响的病因学研究，从而将这些整合在一起。