THE QUANTITATIVE GENETICS OF CLINICAL PSYCHOPATHOLOGY

这是一项为期5年的提案，旨在开发强大的新方法- 精神遗传学具体而言：（1）采取措施， 单主要基因座模型的诊断稳定性， 诊断错误和临床异质性连锁模型 （2）开发同时使用生物化学的模型，或 心理社会措施和潜在变量指数;（3）实施 细胞核数量和质量性状的多元分析 家庭;（4）将随访数据纳入遗传模型中，以允许 在多个时间点进行诊断评估;（5）改变生存率， 用于家庭数据的logistic分析，以纳入不同年龄的 发病和长期趋势纳入遗传和连锁分析;（6）进行 一系列模拟实验来评估不同的实验设计 用于精神病学的遗传学研究;（7）开发高效的计算机程序 （8）将这些新技术应用于 现有数据集的数量，包括情感障碍的研究， 酒精中毒 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， 开展疾病分类学假设检验并解决表型 异质性，开发技术，以检测特定的环境和 遗传因素，为科学家提供记录在案的计算机程序， 社区，并与他人合作，研究广泛的 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， 联系分析将得到解决，这些进展将得到扩大， 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。 这项研究将使更多的病因同质的定义 受影响个体的亚群，特定模式的表征 传播，改善风险预测，发现相关的预 病态特征，并增强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.