THE QUANTITATIVE GENETICS OF CLINICAL PSYCHOPATHOLOGY

这项关于人类种群和数量遗传学的建议将提供 调查精神疾病的有效方法。具体而言：(A) 开发模型以在家庭中同时分析门槛特征 以及相关的定量测量(例如，生化诊断 或心理社会测量)；(B)实施多变量分析 考虑可变家系的家系数量性状 确定结构和方法，并将索引合并到路径中 衡量失序责任构成要素的分析模型； (C)将多因素分离分析扩展到同父异母的兄弟姐妹，以便 检测遗传效应和对儿童的影响，以便将成人和儿童联系起来 精神病理学；(D)将后续数据纳入遗传模型，以 在家庭研究中研究诊断的不可靠性和稳定性；(E)扩大 对家庭数据进行生存分析；(F)调查 家庭相似性的交配和动态模式；和(G)应用这些模式 技术应用于多个家族数据集。 长期目标是发展遗传和非遗传传播 模型是家庭分布的真实表示 精神疾病，开发技术来测试病因学假说和 解决表型异质性，开发技术来检测特定的 环境和遗传因素，提供记录在案的计算机程序以 科学界，并与其他人合作，研究广泛的 精神和内科疾病的谱系。 方法包括理论、计算机实现和模拟，以及 数据分析。首先，遗传流行病学的理论问题将是 解决，然后路径分析和多元模型将被扩展和 数值技术得到了改进。接下来，将执行计算机程序 以及用于评估操作特性的模拟。最后， 方法将应用于数据。 遗传效应在许多精神疾病中都很重要，但 它们与环境相互作用产生疾病的过程是 未知。这项研究将使更多病因的定义成为可能 受影响个体的齐次亚群，其特征 特定的传播模式，改进的风险预测和发现 相关的病前特征。

This proposal in human population and quantitative genetics will provide powerful ways to investigate psychiatric disorders. Specifically to: (a) Develop models to analyze simultaneously in families a threshold character and a correlated quantitative measure (e.g., a diagnosis with a biochemical or psychosocial measure); (b) Implement multivariate analysis of quantitative traits in families taking into account variable family structure and method of ascertainment, and incorporate indices into path analytic models to measure components of the liability for a disorder; (c)\Extend multifactorial segregation analysis to half-siblings in order to detect genetic effects and to children in order to relate adult and child psychopathology; (d) Incorporate follow-up data into genetic models to study diagnostic unreliability and stability in a family study; (e) Extend the use of survival analysis for family data; (f) Investigate assortative mating and dynamic models of familial resemblance; and (g) Apply these techniques to several family data sets. Long term objectives are to develop genetic and non-genetic transmission models which are realistic representations of the familial distributions of psychiatric illneses, develop techniques to test nosological hypotheses and resolve phenotypic heterogeneities, develop techniques to detect specific environmental and genetic factors, provide documented computer programs to the scientific community, and collaborate with others to study a broad spectrum of psychiatric and medical disorders. Methods include theoretical, computer implementation and simulation, and data analysis. First, theoretical issues in genetic epidemiology will be resolved, then path analytic and multivariate models will be extended and numerical techniques improved. Next, computer programs will be implemented and simulations used to assess operating characteristics. Finally, the methods will be applied to data. Genetic effects are important in many psychiatric disorders, but the ways in which they interact with the environment to produce an illness are unknown. This research will enable the definition of more etiologically homogeneous subgroups of affected individuals, the characterization of specific modes of transmission, improved risk prediction, and the discovery of relevant pre-morbid characteristics.