SEGREGATION/LINKAGE ANALYSIS FOR HYPERTENSION

本项目拟继续进行一系列模拟实验 旨在确定最近的功率，鲁棒性和有效性 分离和连锁分析的方法。 特别强调 将被放置在确定的权力和鲁棒性的方法， 隔离分析，包括确定性偏差的校正， 确定未能纠正以下方法的影响（如有）： 或者使用不适当的纠正。 获得的洞察力 将用于分析血液的谱系数据， 血压和其他与高血压相关的变量。 特别努力 将检测主要基因，试图确定遗传 高血压的组成部分。 三种遗传模型的功效、鲁棒性和有效性将被 考虑：1）传输概率模型，2）混合模型，以及 3)统一模型、单位点成分混合模型 根据传输概率进行参数化。 的鲁棒性 每个模型都将考虑环境因素的存在， 偏度和峰度以及其他家族环境相关性。 几种纠正确认偏差的方法将在 根据各种抽样方案（随机， 顺序，先证者抽样框架，“晶体生长”，和单纯形和 多重确定）。 模拟数据将基于参数 来自实际的高血压研究，因此可以得出有效的结论， 从这些实验中得出的结论。 分离和连锁分析的方法是强大和强大的 关于假设的失败（特别是在 实际高血压数据）将应用于由 其他调查员。 主要数据集包括五个大的 每个家系通过一个高血压先证者确定。 的 第二组数据将包括大约10个大谱系 作为博加卢萨心脏研究的一部分随机确定。 长期的 目标包括：1）解剖遗传成分， 高血压，以确定个人与 高血压的遗传易感性，在这些人成为 明显的高血压和2）正在进行的新方法的评估， 分离/连锁分析，用于阐明遗传的本质 件.

This project proposes to continue a series of simulation experiments designed to determine the power, robustness and validity of recently developed methods of segregation and linkage analysis. Special emphasis will be placed on determining the power and robustness of methods of segregation analysis that incorporate corrections for certainment bias and to determine the effect, if any, of failing to correct for the method of ascertainment, or of using an inappropriate correction. Insight gained from these experiments will be used to analyze pedigree data on blood pressure and other variables related to hypertension. A particular effort will be made to detect major genes in an attempt to determine the genetic component of hypertension. The power, robustness and validity of three genetic models will be considered: 1) the transmission probability model, 2) the mixed model, and 3) the unified model, a mixed model with the single locus component parameterized in terms of transmission probabilities. The robustness of each model will be considered with respect to the presence of environmental skewness and kurtosis, and other familial environmental correlations. Several methods of correcting for ascertainment bias will be used in the analysis of data selected according to various sampling schemes (random, sequential, proband sampling frame, "crystal growth", and simplex and multiplex ascertainment). Simulated data will be based on parameters derived from actual hypertension studies, so that valid conclusions can be drawm from these experiments. Methods of segregation and linkage analysis that are powerful and robust with respect to failures of assumptions (particularly those found in the actual hypertension data) will be applied to two sets of data provided by other investigators. The primary set of data comprises five large pedigrees each ascertained through a single hypertensive proband. The second set of data will consist of approximately ten large pedigrees ascertained at random as part of the Bogalusa Heart Study. Long range objectives include 1) the dissection of the genetic component of hypertension with a view to the identification of individuals with a genetic predisposition for hypertension before those individuals become overtly hypertensive and 2) an ongoing evaluation of new methods in segregation/linkage analysis, used to illuminate the nature of genetic components.