Measurement Error in Population Health Inequity Research using Novel Biomeasures-Supplement

说明(申请人提供)：在消除健康差距方面的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，可以检验将环境、心理社会、行为和生物过程联系起来的复杂假设。拟议的项目是一项跨学科的合作努力，整合了人口健康差异、分子生物学和测量误差对与人口健康研究直接相关的参数估计的统计影响方面的专业知识。我们将解决这样一个问题，即来自血液或唾液的DNA与大量基于人口的数据集一起储存在人口健康研究中是否有效-端粒长度(TL)是一种有趣的压力中介健康、发育和衰老的新生物衡量标准--如果是的话，需要多少样本量。对TL的群体差异的研究主要是基于高度精选的、种族相同的、临床的或方便的样本。社会经济措施往往缺乏或很简陋。最先进的测量TL的方法是通过从新鲜静脉血液样本中提取的白细胞来源的DNA。启动新的基于人群的数据收集活动，包括抽血、分子测量和所需的广泛的社会、环境、行为和健康变量，成本高昂，而且需要数年时间才能分析数据。然而，现有的基于人群的数据收集越来越多地分离出血液DNA，以便在使用EB病毒(EBV)转化和永生化细胞或将DNA存储在唾液中后存储在标本储存库中。这两种方法对于TL测量都不是理想的。对于种群研究来说，尚未回答的关键问题是，相对于原始TL或感兴趣的种群，这些TL度量中引入的误差是随机的还是系统性的。我们建议评估使用的有效性 EBV-使血细胞或唾液细胞永生化，以估计TL的群体差异。我们将收集底特律和安娜堡150名成年黑人、白人或墨西哥裔女性的血液和唾液，并使用直接从新鲜血细胞中提取的DNA、从我们将使EBV永生化的细胞中提取的DNA以及从唾液中提取的DNA多次测量每个女性的TL。通过将样本沿着比较的关键轴-种族/民族、社会经济地位、压力水平和邻里关系-进行分层，并在女性内部比较永生化和新鲜血液样本以及新鲜血液样本和唾液之间的TL，我们将直接衡量永生化或组织类型对TL研究结果的有效性和可靠性的影响，这些研究使用保存的样本，以及未来可能使用保存的样本来测试关于人口健康差异的跨学科假设。无论使用永生化血液或唾液细胞来测量TL的有效性得出什么结论，这些发现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.