A STUDY OF SEGREGATION/LINKAGE ANALYSIS FOR HYPERTENSION

该项目计划继续进行一系列模拟实验 旨在确定最近的 发展了分离和连锁分析方法。特别强调 将放在确定方法的能力和健壮性上 分离分析，合并了对确定性偏差和 若要确定未能纠正 查明，或使用不适当的更正。获得洞察力 这些实验将被用来分析血液的谱系数据 压力和其他与高血压相关的变量。一项特别的努力 将被用来检测主要基因，试图确定基因 高血压的组成部分。 三个遗传模型的威力、稳健性和有效性将是 考虑：1)传输概率模型，2)混合模型，以及 3)统一模型，具有单一轨迹分量的混合模型 根据传输概率进行了参数化。的健壮性 每种型号都将考虑到环境因素的存在 偏度和峰度，以及其他家族性环境相关性。 几种纠正确定偏差的方法将用在 分析根据各种采样方案(随机， 顺序采样框架、先导采样框架、“晶体生长”、单纯形和 多路确定)。模拟数据将基于参数 来自于实际的高血压研究，因此有效的结论可以 从这些实验中提取出来的。 功能强大的分离和连锁分析方法 关于假设的失败(特别是在 实际高血压数据)将应用于由 其他调查人员。主要数据集包括五个大的 每个家系都是通过一个高血压先证者确定的。这个 第二组数据将由大约10个大的家系组成 作为博加卢萨心脏研究的一部分随机确定。远距离 目标包括：1)解剖人类的遗传成分 高血压，以期识别患有高血压的个人 高血压的遗传易感性在这些人成为 公开高血压和2)新方法的持续评估 分离/连锁分析，用于阐明遗传的本质 组件。

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.