HUMAN GENETICS RESEARCH

人类遗传学研究

• 批准号: 6200880
• 负责人: JOE C CHRISTIAN
• 金额: $ 21.25万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-12-01 至 2000-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6200880
• 关键词: alcoholic beverage consumption; alcoholism /alcohol abuse; behavioral /social science research tag; behavioral genetics; biomarker; blood tests; breath tests; cognition; drug hypersensitivity; drug resistance; electroencephalography; family genetics; genetic markers; genetic polymorphism; genetic susceptibility; human subject; neuropsychological tests; personality; personality tests; phenotype; psychophysiology; siblings; twin /multiplet; young adult human (21-34)

We propose to identify consistent predictors of reactivity to alcohol challenge based on (a) family history of alcohol abuse, (b) individual behavioral, personality, and cognitive risk factors, and (c) recent drinking history. We will study three samples of young adults: (1) Subjects selected for differential risk based on differences in family history of alcohol abuse; (2) Discordant sibling pairs selected for differential risk, so that one sibling has the heightened profile of behavioral, personality, and cognitive risk factors reported for subjects with a family history of alcohol abuse, while the other sibling shows a low risk profile, similar to subjects with no family history of alcohol abuse; and (3) Monozygotic (MZ) twins assessed for the same risk factors as the first two samples. Exploiting the naturalistic weekend drinking patterns of young adults, all subjects will be tested in alcohol challenge once after several days of drinking, and once after several days abstinence, allowing evaluation of the effects of recent drinking and interactions of those effects with risk status. We will extend previous work on disinhibition as a risk factor for alcohol problems by conducting multi-method assessments of disinhibitory characteristics, and we will evaluate the association of those characteristics with family risk and reactivity to alcohol challenge. The MZ twins will be tested both in our oral dosing protocol and in the clamping protocol proposed by our colleagues at IUSM, providing an estimate of consistency of individual differences in reactivity across protocols, and an upper bound estimate of the heritability of individual differences in risk factors and in the alcohol response patterns assessed in each site. In combination, the three sampling strategies and the within-subject evaluation of recent drinking effects provide an efficient program for evaluating putative markers of genetic risk.

我们建议确定对酒精反应性的一致预测指标 基于（a）酒精滥用家族史的挑战，（b）个人 行为，个性和认知风险因素，以及（c）最近 饮酒史。 我们将研究三个年轻人样本：（1） 基于家庭差异而选择出于差异风险的受试者 酗酒的历史； （2）选择的兄弟姐妹对 差异风险，以便一个兄弟姐妹的概况提高 报告受试者报告的行为，个性和认知风险因素 有了酗酒的家族史，而其他兄弟姐妹则显示 低风险状况，类似于没有酒精家族​​史的受试者 虐待; （3）评估了相同危险因素的单卵（MZ）双胞胎 作为前两个样本。 利用自然主义的周末喝酒 年轻人的模式，所有受试者将在酒精挑战中进行测试 一次喝了几天，几天后一次 禁欲，允许评估最近饮酒的影响 这些影响与风险状态的相互作用。 我们将扩展以前 通过进行抑制作用作为酒精问题的危险因素 多方法评估dis抑制特征，我们将 评估这些特征与家庭风险的关联和 对酒精挑战的反应性。 MZ双胞胎将在我们的 口服给药方案以及我们提出的夹紧协议 IUSM的同事提供了个人一致性的估计 方案之间的反应性差异，以及 个体差异在风险因素和 在每个站点评估的酒精反应模式。 结合 三种抽样策略以及对最近的受试者内评估 饮酒效果提供了一个评估推定的有效计划 遗传风险的标记。