ASSESSING VARIANCE COMPONENTS MODELS ON PEDIGREES

评估谱系的方差分量模型

• 批准号: 3281395
• 负责人: Terri H Beaty
• 金额: $ 9.73万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-07-01 至 1986-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3281395
• 关键词: cell population study; developmental genetics; epidemiology; genetic counseling; genetic models; heterophile antigens; human population genetics; immunoglobulin E; immunoregulation; inborn carbohydrate metabolism disorder; lipid metabolism

Our goal in this project is to develop a systematic approach for estimating genetic and non-genetic components of variance for quantitative traits from pedigree data, while assessing the validity of a given model for the data at hand. Estimating variance components under a general multifactorial model in this manner represents an important early step in the study of possible genetic mechanisms which may underlie the familial aggregation seen in many common diseases. This project will consist of four phases which will complement one another: (1) A rigorous description of the asymtotic properties of multivariate models for pedigrees; (2) Robustness studies of maximum likelihood estimators obtained under these models for finite samples with non-normal distributions; (3) Evaluation of various goodness-of-fit statistics for assessing the goodness and stability of fit to real and simulated data sets; and (4) Application of these three approaches to detect possible etiological heterogeneity (genetic and non-genetic) in sets of pedigrees. This last phase has great potential in studies of many common diseases where no single etiological mechanism can account for the familial aggregation in either the disease or in traits associated with the disease. Two sets of pedigree data will be used to develop and test these techniques: a set of families with serum lipid measurements collected by the Lipid Research Clinic and a set of families with serum IgE measurements collected as part of a study on atopic allergies. Simulated pedigrees will also be used to illustrate selected features of these methods.

我们在这个项目中的目标是开发一种系统的方法来估计 数量性状变异的遗传和非遗传成分 谱系数据，同时评估给定数据模型的有效性 就在手边。 估计一般多因素下的方差分量 这种方式的模型代表了研究的重要早期步骤 可能是家族聚集的潜在遗传机制 见于许多常见疾病。 该项目将分为四个阶段 这将相互补充：（1）严格的描述 谱系多元模型的渐近性质； (2) 稳健性 在这些模型下获得的最大似然估计量的研究 非正态分布的有限样本； (3) 各项评价 用于评估拟合优度和稳定性的拟合优度统计 真实和模拟数据集； (4) 这三者的应用 检测可能的病因异质性（遗传和 非遗传）在谱系集中。 最后一个阶段具有巨大的潜力 对许多常见疾病的研究，没有单一的病因学机制可以 解释疾病或性状的家族聚集 与疾病有关。 两组谱系数据将用于 开发并测试这些技术：一组具有血清脂质的家族 脂质研究诊所和一组家庭收集的测量结果 作为特应性研究的一部分收集的血清 IgE 测量值 过敏。 模拟的血统书也将用于说明选定的 这些方法的特点。

项目成果

Robust inference for variance components models in families ascertained through probands: I. Conditioning on proband's phenotype.

通过先证者确定的家庭中方差分量模型的稳健推断：I.先证者表型的调节。

• 发表时间: 1987
• 影响因子: 2.1
• 作者: Beaty, T H;Liang, K Y
• 通讯作者: Liang, K Y

Genetic analysis of plasma sitosterol, apoprotein B, and lipoproteins in a large Amish pedigree with sitosterolemia.

患有谷甾醇血症的大型阿米什人家系中血浆谷甾醇、脱辅基蛋白 B 和脂蛋白的遗传分析。

• 发表时间: 1986-04
• 影响因子: 9.8
• 作者: Beaty, T H;Kwiterovich Jr, P O;Khoury, M J;White, S;Bachorik, P S;Smith, H H;Teng, B;Sniderman, A
• 通讯作者: Sniderman, A

Variance components analysis of forced expiration in families.

家庭强制终止的方差成分分析。

• 发表时间: 1985-08
• 作者: Astemborski, J A;Beaty, T H;Cohen, B H
• 通讯作者: Cohen, B H