Measurement Error in Population Health Inequity Research using Novel Biomeasures

描述（由申请人提供）：消除健康差距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，可以测试连接环境、社会心理、行为和生物过程的复杂假设。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。我们将解决的问题是，从血液或唾液中提取的DNA与基于大量人口的数据集是否有效地用于端粒长度（TL）的人口健康研究——一个有趣的新的生物测量压力介导的健康、发育和衰老——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性、种族同质性、临床或方便样本。社会经济措施往往是缺失的或基本的。最先进的测量TL的方法是从新鲜静脉血样本中提取白细胞来源的DNA。开展新的基于人口的数据收集活动，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，现有的基于人群的数据收集越来越多地将血液DNA分离出来，在细胞被eb病毒转化和永生后储存在标本库中，或者将DNA储存在唾液中。这两种方法都不是TL测量的理想方法。对于种群研究来说，关键的悬而未决的问题是，这些TL测量中引入的误差是随机的还是系统的，与原始TL或感兴趣的种群有关。我们建议估计使用的有效性

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.