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Measurement Error in Population Health Inequity Research using Novel Biomeasures

a PSC Research Project

Investigators:   Arline T. Geronimus, John Bound, Colter Mitchell

Theory and evidence suggest that social processes work through environmental, psychosocial, physiological, and molecular mechanisms to produce population health disparities. Progress in eliminating disparities requires interdisciplinary efforts among social and biological scientists, and new or improved data sets through which complex hypotheses linking social and biological processes can be tested.
Telomere length (TL) is an intriguing new biomeasure of aging and stress, with growing interest in its use as a marker of the toll that cumulative stress takes on the body. The general state of research on racial/ethnic or socioeconomic differences in TL is rudimentary, usually based on highly select, racially homogeneous, or convenience samples with socioeconomic measures often completely absent in studies of racial variation.
Leukocyte derived DNA from fresh venous blood samples is state-of-the-art for TL measurement; yet, it is labor intensive and very expensive to collect venous blood and also to collect the broad range of socioeconomic, psychosocial, and environmental information on large, representative or community-based samples needed to advance interdisciplinary health disparities research. However, ongoing national data collections isolate blood DNA and bank it in repositories after the cells have been transformed & immortalized using Epstein-Barr virus (EBV). Others collect, store and extract DNA from saliva. Neither is ideal for individual TL measurement. EBV-immortalization activates processes affecting telomere length. Saliva TL is longer than blood leukocyte derived DNA. The critical unanswered question for population research is whether the error introduced is random or systematic with respect to original telomere length or to populations of interest.
We propose to estimate the validity of using EBV-immortalized or saliva cells to estimate population differences in TL. We will draw and analyze blood and saliva from 150 adult black, white, or Mexican origin women 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 and neighborhood -- comparing within-woman results 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 both the validity and reliability of inferences drawn based on using the biomeasures available in large, representative data sets. Findings will have implications that can be applied toward increasing the pace of health disparities research, whatever the conclusion on the validity of using immortalized blood or saliva cells for TL measurement.

Funding Period: 04/15/2014 to 03/31/2017

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