Coming up short: Comparing venous blood, dried blood spots & saliva samples for measuring telomere length in health equity research

Abstract

Background Telomere length (TL) in peripheral blood mononuclear cells (PBMC) from fresh venous blood is increasingly used to estimate molecular impacts of accumulated social adversity on population health. Sometimes, TL extracted from saliva or dried blood spots (DBS) are substituted as less invasive and more scalable specimen collection methods; yet, are they interchangeable with fresh blood? Studies find TL is correlated across tissues, but have not addressed the critical question for social epidemiological applications: Do different specimen types show the same association between TL and social constructs? Methods We integrate expertise in social epidemiology, molecular biology, and the statistical impact of measurement error on parameter estimates. Recruiting a diverse sample of 132 Metro-Detroit women, we measure TL for each woman from fresh blood PBMC, DBS, and saliva. Using regression methods, we estimate associations between social characteristics and TL, comparing estimates across specimen types for each woman. Results Associations between TL and social characteristics vary by specimen type collected from the same woman, sometimes qualitatively altering estimates of the magnitude or direction of a theorized relationship. Being Black is associated with shorter TL in PBMC, but longer TL in saliva or DBS. Education is positively associated with TL in fresh blood, but negatively associated with TL using DBS. Conclusion Findings raise concerns about the use of TL measures derived from different tissues in social epidemiological research. Investigators need to consider the possibility that associations between social variables and TL may be systematically related to specimen type, rather than be valid indicators of socially-patterned biopsychosocial processes.

Effects of DNA extraction, DNA integrity, and laboratory on the precision of qPCR-based telomere length measurement - a multi-lab impartial study

“…Systematic testing of the effect of different DNA extraction protocols on TL precision measured from different tissue sources has not been done. However, our results are consistent with reported differences in TL and precision measured in saliva, peripheral blood mononuclear cells (PBMCs) and dried bloods spots (DBS) from the same individual, where salting out DNA extraction was utilized for saliva extraction but Purelink, a silica membrane-based kit, was utilized for the DBS and PBMCs (21). Studies seeking to determine the true correlation of TL measured from different tissue sources in the same individual will need to address variation induced by different DNA extraction protocols.…”

Promising applications of human-derived saliva biomarker testing in clinical diagnostics

“…Another research showed that telomere length was longer in saliva than in blood. 62 Cell free DNA (cfDNA) After apoptosis or necrosis, cell debris including nucleotides releases into the interstitial fluid. Thus, individuals with a high rate of cell death tend to have a higher proportion of cfDNA.…”

Telomere Length among Chinese Aged 75+ Years

“…[14][15][16][17]. Some research groups even suggested that previously reported associations between TL and social factors might only represent a systemic bias instead of a real association [18]. A recent paper used qPCR methods in UK Biobank samples and found that the variance due to technical factors was huge.…”