Use of telomere length (TL) as a biomarker for various environmental exposures and diseases has increased in recent years. Various methods have been developed to measure telomere length. Polymerase chain reaction (PCR)-based methods remain wide-spread for population-based studies due to the high-throughput capability. While several studies have evaluated the repeatability and reproducibility of different TL measurement methods, the results have been variable. We conducted a literature review of TL measurement cross-method comparison studies that included a PCR-based method published between January 1, 2002 and May 25, 2020. A total of 25 articles were found that matched the inclusion criteria. Papers were reviewed for quality of methodologic reporting of sample and DNA quality, PCR assay characteristics, sample blinding, and analytic approaches to determine final TL. Overall, methodologic reporting was low as assessed by two different reporting guidelines for qPCR-based TL measurement. There was a wide range in the reported correlation between methods (as assessed by Pearson’s r) and few studies utilized the recommended intra-class correlation coefficient (ICC) for assessment of assay repeatability and methodologic comparisons. The sample size for nearly all studies was less than 100, raising concerns about statistical power. Overall, this review found that the current literature on the relation between TL measurement methods is lacking in validity and scientific rigor. In light of these findings, we present reporting guidelines for PCR-based TL measurement methods and results of analyses of the effect of assay repeatability (ICC) on statistical power of cross-sectional and longitudinal studies. Additional cross-laboratory studies with rigorous methodologic and statistical reporting, adequate sample size, and blinding are essential to accurately determine assay repeatability and replicability as well as the relation between TL measurement methods.

No abstract

Use of telomere length (TL) as a biomarker for various environmental exposures and diseases has increased in recent years. Various methods have been developed to measure telomere length. PCR-based methods remain wide-spread for population-based studies due to the high-throughput capability. While several studies have evaluated TL measurement methods, the results have been variable.   We conducted a literature review of TL measurement cross-method comparison studies that included a PCR-based method published between January 1, 2002 and May 25, 2020. A total of 20 articles were found that matched the inclusion criteria. Papers were reviewed for quality of methodologic reporting of sample and DNA quality, PCR assay characteristics, and analytic approaches to determine final TL was low as assessed by two different recommended reporting guidelines. Additionally, few papers reported whether samples were blinded for analysis. Reported correlation between methods (as assessed by Pearson’s r) varied, as did reported coefficients of variation or intra-class correlation coefficient. The sample size for nearly all studies was less than 100, raising significant concerns about statistical power. Overall, this review found that the current literature on the relation between TL measurement methods is lacking in validity and scientific rigor. To assist future investigators, we present recommendations for reporting guidelines of PCR-based TL measurement methods and present data to demonstrate the impact of assay variability on statistical power. Future cross-laboratory studies with rigorous methodologic and statistical reporting, adequate sample size, and blinding are essential to determine the true relation and variability of various TL measurement methods and are a key directive to the newly initiated Telomere Research Network funded jointly by then NIA and NIEHS.