Telomere length associates with chronological age and mortality across racially diverse pulmonary fibrosis cohorts

Adegunsoye, Ayodeji; Newton, Chad A.; Oldham, Justin M.; Ley, Brett; Lee, Cathryn T.; Linderholm, Angela L.; Chung, Jonathan H.; Garcia, Nicole; Zhang, Da; Vij, Rekha; Guzy, Robert; Jablonski, Renea; Bag, Remzi; Voogt, Rebecca S.; Shwu-Fan, Ma.; Sperling, Anne I.; Raghu, Ganesh; Martinez, Fernando J.; Strek, Mary E.; Wolters, Paul J.; Garcia, Christine Kim; Pierce, Brandon L.; Noth, Imre

doi:10.6082/sn5md-c7s17

Published March 17, 2023 | Version v1

Journal article Open

Telomere length associates with chronological age and mortality across racially diverse pulmonary fibrosis cohorts

1. University of Chicago
2. University of Texas Southwestern
3. University of California, Davis
4. University of California, San Francisco
5. Columbia University
6. University of Virginia
7. University of Washington
8. Weill Cornell Medicine

Pulmonary fibrosis (PF) is characterized by profound scarring and poor survival. We investigated the association of leukocyte telomere length (LTL) with chronological age and mortality across racially diverse PF cohorts. LTL measurements among participants with PF stratified by race/ethnicity were assessed in relation to age and all-cause mortality, and compared to controls. Generalized linear models were used to evaluate the age-LTL relationship, Cox proportional hazards models were used for hazard ratio estimation, and the Cochran–Armitage test was used to assess quartiles of LTL. Standardized LTL shortened with increasing chronological age; this association in controls was strengthened in PF (R = −0.28; P < 0.0001). In PF, age- and sex-adjusted LTL below the median consistently predicted worse mortality across all racial groups (White, HR = 2.21, 95% CI = 1.79–2.72; Black, HR = 2.22, 95% CI = 1.05–4.66; Hispanic, HR = 3.40, 95% CI = 1.88–6.14; and Asian, HR = 2.11, 95% CI = 0.55–8.23). LTL associates uniformly with chronological age and is a biomarker predictive of mortality in PF across racial groups.

Data availability

All data supporting the findings described in this manuscript are available in the article and in the Supplementary Information and from the corresponding author upon request. Source data are provided with this paper. The processed telomere length data for the HRS control population are available at "hrsdata" with the identifier [https://hrsdata.isr.umich.edu/data-products/2008-telomere-data]. Response to data requests will be made within 6–8 weeks of receipt. The pulmonary fibrosis telomere length data that support the findings of this study are subject to controlled access via data use agreements due to reasons of clinical human data sensitivity and are available upon reasonable request from the corresponding author [A.A.].

Code for data cleaning and analysis is provided as part of the replication package. It is available at https://doi.org/10.5281/zenodo.7431322.

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