MARC: Genetic Epidemiology of Alcoholism & Comorbidity

描述（由申请人提供）：这是多站点中西部酒精中毒研究中心（MARC）的第一个竞争延续。我们研究的广泛重点是社区（而不是临床确定）样本中酒精问题和相关合并症的病因学和病程，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，并特别关注青少年和青年。MARC的组织结构如下：(i)行政核心，由MARC主任Heath和科学与行政联合主任Sher和Bucholz领导，负责协调基于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，以及基于MARC的研究项目的评估、确定、数据管理和方法支持；（ii）四项研究；（三）开展试点，以促进新的酒精研究人员的发展，并为现有的研究人员指明新的方向。本研究包括四个部分。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）或烟草效应（生理性震颤）敏感性的相互作用。其次，使用双胞胎的孩子范式来调查母亲酗酒的环境后果的影响，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（遗传风险高，环境风险高）的后代，要么是未受影响的母亲(a)可能有一个酗酒的同卵双胞胎姐妹（遗传风险也高，但环境风险降低）。或(b)嗜酒异卵双胞胎姐妹（中等遗传风险，低环境风险），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，通过增加分子遗传成分，扩展正在进行的4项研究，这些研究前瞻性地跟踪了从青春期到青年期的样本，以调查候选基因对风险影响的发育展开。第四，寻求弥合酒精和烟草共病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，作为酒精和烟草使用共病及其动机后遗症的生态学研究，通过电子日记进行评估。综上所述，我们希望在多个分析水平上推进基因型x环境相互作用对酒精中毒风险的病因学研究。

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.