ASSESSING THE IMPACT OF GLOBAL VERSUS LOCAL ANCESTRY IN ASSOCIATION STUDIES

评估全球血统与当地血统在协会研究中的影响

• 批准号: 7956499
• 负责人: XIAOFENG ZHU
• 金额: $ 0.97万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7956499
• 关键词: Accounting; Address; Adult; American; Chromosomes; Computer Retrieval of Information on Scientific Projects Database; Data; European; Funding; Genome; Genotype; Grant; Height; Human Genetics; Individual; Institution; Measures; Performance; Population; Principal Component Analysis; Research; Research Personnel; Residual state; Resources; Single Nucleotide Polymorphism; Source; Stratification; Testing; United States National Institutes of Health; cohort; genetic analysis; genome wide association study; genome-wide; offspring

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. To account for population stratification, principal components analysis is often performed using single nucleotide polymorphisms (SNPs) across the genome. We used Framingham GAW16 data to compare the performance of local ancestry, measured by principal components (PCs) estimated from SNPs in a local chromosomal region, with global ancestry, measured by PCs estimated from genome-wide SNPs, to address underlying population stratification. Standardized height residuals from unrelated adults from the Framingham Offspring Cohort were averaged from longitudinal data. PCs of SNP genotype data were calculated to represent individual's ancestry either 1) globally using all SNPs across the genome or 2) locally using SNPs in adjacent 20 Mbp regions within each chromosome. We assessed the extent to which there are differences in association studies of height depending on whether PCs for global, local or both are included as covariates.The correlations between local and global PCs were low (r < 0.12), suggesting variability between local and global ancestry estimates. Q-Q plots of the p values from genome-wide association tests indicate inflated type I error rate without adjusting for ancestry, but can be reasonably controlled by adjusting for local ancestry, global ancestry, or both. Spurious associations are observable in this European-American population and the effect of population stratification in association analysis can be controlled by adjustment with local or global ancestry PCs. Population stratification is a potential source of bias in this seemingly homogenous Framingham population. However, local and global PCs derived from SNPs appear to provide adequate information about ancestry.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 为了解释群体分层，通常使用整个基因组的单核苷酸多态性 (SNP) 进行主成分分析。 我们使用 Framingham GAW16 数据来比较本地血统（通过根据局部染色体区域的 SNP 估计的主成分 (PC) 测量）与全球血统（通过根据全基因组 SNP 估计的 PC 测量）的性能，以解决潜在的群体分层问题。来自弗雷明汉后代队列的无关成年人的标准化身高残差根据纵向数据进行平均。 计算 SNP 基因型数据的 PC 来代表个体的祖先，1）全局使用基因组中的所有 SNP，或 2）局部使用每条染色体内相邻 20 Mbp 区域中的 SNP。 我们根据是否将全局、局部或两者的 PC 作为协变量来评估身高关联研究中存在差异的程度。局部和全局 PC 之间的相关性较低 (r < 0.12)，表明局部和全局血统估计之间存在差异。 来自全基因组关联测试的 p 值的 Q-Q 图表明，在不调整血统的情况下 I 型错误率夸大，但可以通过调整局部血统、全球血统或两者来合理控制。在这个欧美人口中可以观察到虚假关联，并且关联分析中人口分层的影响可以通过调整本地或全球血统 PC 来控制。 人口分层是看似同质的弗雷明汉人口的潜在偏差来源。 然而，源自 SNP 的本地和全球 PC 似乎提供了有关血统的充分信息。