Measurement Error in Population Health Inequity Research using Novel Biomeasures

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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.