Molecular Epidemiology of Alcoholism 3 - EDAC Families

描述(由申请人提供)：此IRPG申请寻求支持 研究计划定位导致重型肝炎变异的基因 饮酒和酒精(以及相关的烟草)依赖风险，使用 从普通人群中确定具有流行病学信息的样本 对澳大利亚和美国越战时期的双胞胎登记员及其家庭的调查 会员。IRPG组件IRPG3提出了一种400标记的10 cM基因组扫描 在目标N=600上使用EDAC(极端不协调和协调)方法 澳大利亚的兄弟姐妹，预计总数为2400人。兄弟会 根据大量饮酒的量化指标进行选择，该指标已在 这个社会表现出(I)高遗传率(45%-52%)，在整个 酒精消费水平的范围，这不是遗传造成的 精神病、社会人口学、体重指数或其他危险因素；高 与酒精依赖风险的遗传相关性(0.82)以及 尼古丁依赖度(0.72)；连续且近似正态分布 在人群中；重测信度高(0.74-0.81 相关性)。将通过诊断确定信息丰富的兄弟姐妹关系 采访有酗酒史的先证者的全部兄弟姐妹 依赖，或在定量指数上的分数超过85% 饮酒。目标600个兄弟姐妹：(I)每个兄弟姐妹将包含两个兄弟姐妹 他们要么不和谐(一个低于30%，一个高于第85个百分位数 百分位数)或高度协调(两者都在第85个百分位数的高位)； 包括关于其他兄弟姐妹的数据；以及(Iii)将包括所有可用的 亲生父母。我们将获取血液样本，诊断性面谈数据 终生酒精依赖、吸烟和烟草依赖史，以及 相关精神危险因素(严重抑郁史、焦虑史 精神障碍、儿童品行障碍)和一生的量化指标 饮酒量最大和最大的时期。来自目标600的数据 IRPG3兄弟关系，以及从以下各项中选择的其他信息丰富的兄弟关系 约600对同胞符合重度吸烟的基因组扫描 将从已经资助的研究中获得(因此，其中许多将是 对于大量酒精消费的协调性)将使用Robust， 无模型多点连杆分析技术，以及在关节连杆中 二元酒(或尼古丁)依赖与定量酒分析 消费表型。

DESCRIPTION (provided by applicant): This IRPG application seeks support for a research program to localize genes that contribute to variation in heavy drinking and alcohol (and associated tobacco) dependence risk, using epidemiologically informative samples ascertained from general population surveys of the Australian and U.S. Vietnam-Era Twin Registers and their family members. This IRPG component, IRPG3, proposes a 400 marker 10cM genome scan using an EDAC (extreme-discordant and concordant) approach on a targeted N=600 Australian sibships, for an expected total of 2400 individuals. Sibships will be selected on a quantitative index of heavy drinking that has been show in this society to exhibit (i) high heritability (45-52 percent), throughout the range of alcohol consumption levels, that is not accounted for by inherited psychiatric, sociodemographic, body-mass index or other risk factors; high genetic correlation with alcohol dependence risk (0.82) as well as with nicotine dependence (0.72); a continuous and approximately normal distribution in the population; high test-retest reliability (0.74-0.81 retest correlations). Informative sibships will be identified via diagnostic interviews with full siblings of probands with either a history of alcohol dependence, or with scores above the 85 percentile on a quantitative index of alcohol consumption. The targeted 600 sibships: (i) will each contain two sibs who are either discordant (one below the 30th percentile and one above the 85th percentile) or high-concordant (both in the upper 85th percentile); (ii) will include data on additional siblings; and (iii) will include all available biological parents. We will obtain blood samples, diagnostic interview data on lifetime history of alcohol dependence, smoking and tobacco dependence, and associated psychiatric risk-factors (history of major depression, anxiety disorders, childhood conduct disorder) and quantitative indices of lifetime maximum and heaviest period alcohol consumption. Data from the targeted 600 IRPG3 sibships, plus additional informative sibships selected from among approximately 600 sib pairs concordant for heavy smoking for whom genome scan will be available from an already funded study (many of whom will therefore be concordant for heavy alcohol consumption) will be analyzed using robust, model-free multipoint linkage analysis techniques, and in joint linkage analysis of binary alcohol (or nicotine) dependence and quantitative alcohol consumption phenotypes.