Quantile regression of the relationship between demographic factors and leukocyte telomere length, measured by Southern blot and qPCR.

Telomere length (TL) is associated with health outcomes. Southern Blotting (SB) is the gold standard of TL measurements, while qPCR-based TL measurements are the most used because of their high throughput. We compared leukocyte TL (LTL) measurements by SB and qPCR, and their ability to capture LTL associations with demographic factors. This study included 908 healthy donors for hematopoietic cell transplantation who had blood samples and data available at CIBMTR®. We used quantile regression (QR) to assess the associations between selected demographic factors and LTL across the LTL distribution. Pearson correlation coefficient and Bland-Altman plot were used to compare SB-LTL and qPCR-LTL measurements. SB-LTL and qPCR-LTL were modestly correlated (r = 0.58, P < 0.001). On average, SB-LTL shortened by 29 base pairs (bp) per year and was 190 bp longer in females than in males. QR analyses showed that the association between SB-LTL and age varied across the LTL distribution, with stronger age-related shortening at higher percentiles (25 bp at the 25th percentile vs. 31 bp at the 75th percentile; P = 0.003). Females had longer SB-LTL than males across all percentiles (P < 0.05 in SB-LTL analysis), and the magnitude of this sex difference did not vary significantly across the LTL distribution (157 bp at the 25th percentile vs. 221 bp at the 75th percentile; P = 0.33). Both SB and qPCR showed an inverse relationship between LTL and age, though the magnitudes differed between methods. Considering the full LTL distribution in studies of lifestyle factors and diseases may provide better molecular insights and guide LTL utilization in health applications.