THE QUANTITATIVE GENETICS OF CLINICAL PSYCHOPATHOLOGY

这一建议在人类群体和数量遗传学将提供 研究精神疾病的有效方法 特别是：（a） 开发模型，同时分析家庭中的阈值特征 以及相关的定量测量（例如，一个生化诊断 （B）实施多变量分析， 计及可变家系的家系数量性状 结构和确定方法，并将指标纳入路径 分析模型，以衡量一个障碍的责任组成部分; (c)将多因素分离分析扩展到半同胞， 检测遗传效应和儿童，以便将成人和儿童联系起来 （d）将后续数据纳入遗传模型， 研究家庭研究中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 交配和动态模型的家族相似性;和（g）应用这些 几个家庭数据集的技术。 长期目标是发展遗传和非遗传传播 模型是家庭分布的现实表示， 精神疾病，发展技术来测试疾病分类假设， 解决表型异质性，开发检测特定 环境和遗传因素，提供记录的计算机程序， 科学界，并与其他人合作，研究广泛的 一系列精神和医学疾病。 方法包括理论，计算机实现和模拟， 数据分析 首先，遗传流行病学的理论问题将是 解决，然后路径分析和多变量模型将得到扩展， 数字技术得到改善。 接下来，计算机程序将被实施 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很重要，但 它们与环境相互作用产生疾病的过程 未知 这项研究将使更多的病因定义 受影响个体的同质亚组， 特定的传播模式，改进的风险预测，以及 相关的发病前特征

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.