Measurement Error in Population Health Inequity Research using Novel Biomeasures

在消除健康差距方面取得进展需要社会和生物科学家之间的跨学科努力，以及基于人口的数据集，通过这些数据集可以测试连接环境，心理社会，行为和生物过程的复杂假设。拟议的项目是一个跨学科的合作努力，整合人口健康差异，分子生物学，和测量误差对参数估计直接相关的人口健康研究的appropriticl影响的专业知识。我们将讨论的问题是，是否从血液或唾液中提取的DNA与大量基于人群的数据库一起用于端粒长度（TL）的人群健康研究是有效的-一种有趣的新的压力介导的健康，发育和衰老的生物测量方法-如果是这样，需要多大的样本量。 对TL人群差异的研究主要基于高度选择的、种族同质的、临床的或方便的样本。社会经济措施往往不存在或不完善。测量TL的最先进方法是通过从新鲜静脉血样品中提取的白细胞衍生的DNA。启动新的基于人群的数据收集活动，包括抽血，分子测量以及所需的广泛的社会，环境，行为和健康变量，成本高昂，需要数年时间才能分析数据。然而，现存的基于人群的数据收集越来越多地分离血液DNA，以便在细胞已经使用EB病毒（EBV）转化和永生化或将DNA储存在唾液中之后储存在标本库中。这两种方法都不是理想的TL测量。人口研究的关键问题是，这些TL措施中引入的误差是随机的还是系统的，相对于原始TL或感兴趣的人口。 我们建议估计使用的有效性 EBV永生化血细胞或唾液细胞来估计TL的群体差异。我们将收集来自底特律和安阿伯的150名成年黑人、白色或墨西哥裔妇女的血液和唾液，并使用直接从新鲜血细胞中分离的DNA、从我们将使EBV永生化的细胞中分离的DNA和从唾液中提取的DNA多次测量每个妇女的TL。通过沿着比较的关键轴--种族/民族、社会经济地位、压力水平和邻居--对样本进行沿着分层，并在永生化样本和新鲜血液样本之间以及新鲜血液样本和唾液之间进行关于TL的女性内比较，我们将直接测量永生化或组织类型对使用储存标本的TL研究结果的有效性和可靠性以及对未来的影响潜在的使用存储的标本测试跨学科的假设，人口健康的差距。无论使用永生化血液或唾液细胞测量TL的有效性的结论如何，研究结果都可以应用于加快健康差异研究的步伐。

DESCRIPTION (provided by applicant): Progress in eliminating health disparities requires interdisciplinary efforts among social and biological scientists, and population-based data sets through which complex hypotheses linking environmental, psychosocial, behavioral and biological processes can be tested. The proposed project is an interdisciplinary collaborative effort integrating expertise in population health disparities, molecular biology, and the statisticl impact of measurement error on parameter estimates directly pertinent to population health research. We will address the question of whether DNA from blood or saliva banked with large population based data sets is valid for use in population health studies of telomere length (TL) - an intriguing new biomeasure of stress- mediated health, development, and aging -- and, if so, what sample sizes are needed. Research on population differences in TL is largely based on highly select, racially homogeneous, clinical, or convenience samples. Socioeconomic measures are often absent or rudimentary. The state-of-the-art approach to measuring TL is via leukocyte-derived DNA extracted from fresh venous blood samples. Launching new population-based data collection activities that include blood draws, molecular measurements and the broad swath of social, environmental, behavioral, and health variables needed is costly and takes years before data can be analyzed. However, extant population-based data collections are increasingly isolating blood DNA for storage in specimen repositories after the cells have been transformed and immortalized using Epstein-Barr Virus (EBV) or storing DNA in saliva. Neither approach is ideal for TL measurement. The critical unanswered question for population research is whether the error introduced in these TL measures is random or systematic with respect to original TL or to populations of interest. We propose to estimate the validity of using EBV-immortalized blood cells or saliva cells to estimate population differences in TL. We will collect blood and saliva from 150 adult black, white, or Mexican-origin women in Detroit and Ann Arbor and measure each woman's TL multiple times using DNA directly isolated from fresh blood cells, DNA isolated from cells that we will EBV- immortalize, and DNA extracted from saliva. By stratifying the sample along key axes of comparison - race/ethnicity, socioeconomic status, stress- level, and neighborhood - and making within-woman comparisons on TL between immortalized and fresh blood samples, and between fresh blood samples and saliva, we will directly gauge the effect that immortalization or tissue type has on the validity and reliability o findings from TL studies that use stored specimens and on the future potential use of stored specimens for testing interdisciplinary hypotheses on population health disparities. Findings can be applied toward increasing the pace of health disparities research, whatever the conclusion on the validity of using immortalized blood or saliva cells to measure TL.