QUANTITATIVE GENETICS OF CLINICAL PSYCHOPATHOLOGY

描述（改编自申请人的摘要）：这是一个重新提交的 一个为期五年的应用程序，以开发强大的精神病学方法， 遗传学 具体为：（1）纳入诊断稳定性模型 遗传模型，以允许诊断错误的明确建模， 连锁分析中的临床异质性;（2）实施程序， 细胞核数量性状和质量性状的多元分析 家庭;（3）将随访数据分析纳入遗传模型 允许在多个时间点进行诊断评估;（4） 调查MOD评分（最大化lod评分）在连锁中的效用 复杂性状的分析。 这一目标遵循广泛的模拟研究， MOD评分方法在检测一个人的连锁方面表现最好， 寡基因性状，现在需要进一步的理论工作 探索;（5）研究使用关联的最佳方式， 遗传标记和一旦检测到基因就定位基因的性状;（6） 开发有效的计算机程序来执行这些程序，并添加 他们到我们的计算机图书馆，并应用这些新技术，以一些 现有的数据集，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、计算机实现和模拟以及数据 分析. 第一，遗传流行病学和联系的理论问题 分析将得到解决，这些进步将得到扩展， 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。 这项研究将使更多的病因同质的定义 受影响的个人的亚群，具体模式的特点， 传播，改善风险预测，发现相关的发病前 特色 研究还应加大联动力度 分析以检测异常基因。

DESCRIPTION (Adapted from applicant's abstract): This is a resubmission of a five year application to develop powerful methodologies in psychiatric genetics. Specifically to: (1) incorporate models of diagnostic stability into the genetic models to permit explicit modeling of diagnostic error and clinical heterogeneity within linkage analyses; (2) implement procedures for the multivariate analysis of quantitative and qualitative traits in nuclear families; (3) incorporate the analysis of follow-up data into genetic models to allow for diagnostic evaluations at multiple points in time; (4) investigate the utility of the MOD score (maximized lod score) in linkage analyses of complex traits. This aim follows extensive simulation study in which the MOD score method performed the best for detecting linkage for an oligogenic trait, and theoretical work is now needed for further exploration; (5) examine the optimal way to use association between a genetic marker and a trait to localize genes once they are detected; (6) develop efficient computer programs which implement these procedures and add them to our computer library and apply these new techniques to a number of currently existing data sets, including studies of Affective Disorder 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, 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. The research should also increase the power of linkage analysis to detect abnormal genes.