THE QUANTITATIVE GENETICS OF CLINICAL PSYCHOPATHOLOGY

这是一份为期5年的建议书，旨在开发强大的新方法 精神遗传学。具体到：(1)纳入下列措施 单主轨迹模型的诊断稳定性，以允许显式 连锁诊断误差与临床异质性的建模 分析；(2)开发同时使用生化的模型，或 心理社会测量和潜在变量指数；(3)实施 核材料数量性状和质量性状的多变量分析 家庭；(4)将后续数据纳入遗传模型，以便 多个时间点的诊断评估；(5)修改存活率和 用于纳入可变年龄的家庭数据的Logistic分析 将发病和长期趋势纳入遗传和连锁分析；(6)执行 评估不同实验设计的一系列模拟实验 用于精神病学的遗传学研究；(7)开发有效的计算机程序 实现这些程序；(8)将这些新技术应用于 现有数据集的数量，包括对情感障碍和 酗酒。 长期目标是发展现实的遗传和非遗传 精神疾病家族分布的传播模型， 开发病因学假说的测试并解决表型 异质性，开发技术来检测特定环境和 遗传因素，为科学家提供记录在案的计算机程序 社区，并与其他人合作研究广泛的 精神疾病和内科疾病。 方法包括理论、计算机实现和模拟，以及 数据分析。第一，遗传流行病学的理论问题和 连锁分析将得到解决，然后这些进展将得到推广和 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。 这项研究将使更多病因同质性的定义成为可能 受影响个体的亚群，特定模式的特征 传播，改进了风险预测，发现了相关的预 病态特征，增强了连锁分析的检测能力 异常基因。

This is a 5 year proposal to develop powerful new methodologies -in psychiatric genetics. Specifically to: (1) incorporate measures of diagnostic-stability into the Single Major Locus Model to permit explicit modeling of diagnostic error and clinical heterogeneity in linkage analysis; (2) develop models for the simultaneous use of biochemical, or psychosocial measures, and indices of latent variables; (3) implement the multivariate analysis of quantitative and qualitative traits in nuclear families; (4) incorporate follow-up data into genetic models to allow for diagnostic evaluations at multiple points in time; (5) modify survival and logistic analyses for use in family data to incorporate variable age of onset and secular trends into genetic and linkage analyses; (6) perform a series of simulation experiments to evaluate different experimental designs for genetic studies in psychiatry; (7) develop efficient computer programs which implement these procedures; (8) apply these new techniques to a number of existing data sets, including studies of Affective Disorders and Alcoholism. Long term objectives are to develop realistic genetic and non-genetic transmission models of the familial distributions of psychiatric illness, develop tests of 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 and linkage analysis will be resolved, these advances will then 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. This research will enable the definition of more etiologically homogeneous subgroups of affected individuals, the characterization of specific modes of transmission, improved risk prediction, the discovery of relevant pre- morbid characteristics, and enhance the power of linkage analysis to detect abnormal genes.