QUANTITATIVE GENETIC STUDY OF LRC FAMILY DATA

拟议的研究开发并应用了适当的方法来 主基因座的检测及遗传和家系的分辨 环境对几种对冠心病有重要意义的表型的影响 疾病(CHD)，包括血脂和脂蛋白浓度。 在五家血脂研究诊所(LRC)收集的家庭数据 由国家心肺血液研究所(NHLBI)建立的 被分析。将为这些家庭开发新的统计方法 通过血脂水平升高的先证者确诊(非随机 样本)，并将以统一方式对所有数据进行分析。 将对两个家族的遗传方式进行调查 具有相当临床意义的血脂异常：家族性 合并高脂血症和家族性原发低脂蛋白血症 已知与早产儿冠心病相关的条件。随机使用这两个 和非随机确定的数据，我们将特别调查 在这些情况下，可能存在主基因效应。 具体的假设将在文化和文化层面上制定和检验 生物效应，LRC之间的异质性(识别特定的 这种异质性的来源)，家庭基础之间的联系 多个风险因素，以及家庭相似性的时间趋势(即， 遗传力的年龄相关变异)。它们将使用以下公式进行表述 适当的路径模型。 这项拟议的研究有望显著提高我们对 表型之间的家族关联和相互作用，以及 提供对家庭环境影响的系统评估 不同的人群。这项建议的两个独特之处是 对家庭随机和非随机样本的创新处理 数据，并使用最先进的模型和统计方法。它 应该澄清的是，这项建议只是补充，而不是 重复，在中央病人登记处和 位于教堂山的地方资源中心协调中心。据信，这一点 经济高效的公共卫生研究将扩大对一个巨大的、 昂贵、足智多谋和以前收集的数据集。

The proposed research develops and applies appropriate methodology for the detection of major loci and the resolution of genetic and familial environmental effects on several phenotypes of importance to coronary heart disease (CHD), including plasma lipids and lipoprotein concentrations. Family data collected at five of the Lipid Research Clinics (LRCs) established by the National Heart, Lung, and Blood Institute (NHLBI) will be analyzed. New statistical methods will be developed for the families ascertained through probands with elevated lipid levels (non-random samples), and analyses will be performed on all data in a unified manner. Modes of inheritance will be investigated for two familial dyslipoproteinemias of considerable clinical significance: familial combined hyperlipidemia and familial primary hypoalphalipoproteinemia, two conditions known to be associated with premature CHD. Using both randomly and non-randomly ascertained data, we will especially investigate the possible major gene effects on these conditions. Specific hypotheses will be formulated and tested on the cultural and biological effects, heterogeneity among the LRCs (identifying the specific sources of such heterogeneity), familial basis for associations among the multiple risk factors, and temporal trends in family resemblance (i.e., age-dependent variation in heritabilities). They will be formulated using appropriate path models. The proposed research is expected to improve significantly our knowledge of the familial associations and interactions among the phenotypes, and to provide a systematic assessment of the familial environmental effects in diverse populations. The two unique features of this proposal are the innovative handling of both the random and non-random samples of family data, and the use of state-of-the-art models and statistical methods. It should be clarified that this proposal only complements, and does not duplicate, the ongoing efforts at the Central Patient Registry and Coordinating Center for the LRCs in Chapel Hill. It is believed that this cost-effective Public Health Research will expand understanding of a huge, expensive, resourceful, and previously collected data set.