QUANTITATIVE GENETIC STUDY OF LRC FAMILY DATA

LRC家系数据的定量遗传学研究

• 批准号: 3346440
• 负责人: DABEERU C RAO
• 金额: $ 17.08万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-07-07 至 1990-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3346440
• 关键词: blood vessel disorder; congenital blood protein disorder; human population genetics; hypolipoproteinemia; lipoprotein disorder

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.

拟议的研究开发和应用适当的方法， 检测主要基因座和解决遗传和家族性 环境对冠心病几种重要表型的影响 疾病（CHD），包括血脂和脂蛋白浓度。 在5家脂质研究诊所（LRC）收集的家族数据 由国家心脏，肺和血液研究所（NHLBI）建立， 被分析。 将为家庭制定新的统计方法 通过血脂水平升高的先证者确定（非随机 样本），并将以统一的方式对所有数据进行分析。 遗传方式将调查两个家庭 具有重要临床意义的异常脂蛋白血症：家族性 合并高脂血症和家族性原发性低α脂蛋白血症，两种 已知与早发CHD相关的疾病。 随机使用两者 和非随机确定的数据，我们将特别研究 可能的主要基因对这些条件的影响。 具体的假设将制定和测试的文化和 生物效应，LRC之间的异质性（确定特定的 这种异质性的来源）， 多个风险因素和家族相似性的时间趋势（即， 遗传力的年龄依赖性变化）。 它们将使用 合适的路径模型。 这项拟议中的研究有望大大提高我们对以下问题的认识： 表型之间的家族关联和相互作用，以及 对家庭环境影响进行系统评估， 不同的人群。 该提案的两个独特之处是： 创新处理随机和非随机样本的家庭 数据，以及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，在中央病人登记处正在进行的努力， 位于查佩尔山的LRC协调中心。 据信这 具有成本效益的公共卫生研究将扩大对巨大的， 昂贵的，资源丰富的，以前收集的数据集。