# Genomic Basis of Telomere Length Regulation and Consequences for Complex Traits

> **NIH NIH R56** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2024 · $430,101

## Abstract

PROJECT SUMMARY
Telomere length is considered a good biomarker of organismal and cellular aging. Telomeres get progressively
shorter with each cell division and rates of cellular turnover vary from cell type to cell type and tissue to tissue.
When telomeres become critically short, cells arrest their proliferation and go into senescence resulting in
tissue dysfunction. Telomere length and the rate of telomere shortening shows a great deal of interindividual
variability and is dependent on many factors including genetics, age, environment, and lifestyle. Several age-
related diseases have been associated with telomere shortening including pulmonary fibrosis, COPD, liver
fibrosis, aplastic anemia, myelodysplastic syndrome, Alzheimer’s disease, Parkinson’s disease, myocardial
hypertrophy, dilated cardiomyopathy, ischemia-reperfusion injury, chronic kidney disease, kidney fibrosis,
osteoporosis, and osteoarthritis. The effect of genetics on telomere length has been estimated to be 35-85%
and at least 17 genes have been reported to regulate telomere length and cause telomere biology disorders
(TBD) when disrupted (DKC1, TERC, TERT, NOP10, NHP2, TINF2, WRAP53, CTC1, RTEL1, PARN, ACD,
POT1, NAF1, STN1, ZCCHC8, RPA1, and DCLRE1B). These genes do not explain all cases of TBD and more
telomere length regulators have yet to be characterized. Our proposal is in response to NOT-AG-23-020, which
is meant “to encourage the use of existing cohorts and datasets for well-focused secondary analyses” to
address critical questions in aging research. We have designed our proposal to harness the unique large data
resources at Vanderbilt University Medical Center (VUMC), including idiopathic pulmonary fibrosis (IPF) and
BioVU, and the large public data resources (GTEx consortium, All of Us, and the UK Biobank). We will
reanalyze these datasets, combining multi-omics modeling and phenome-scale interrogation, to identify new
genes and variants responsible for telomere shortening, telomere disease risk, premature aging, and their
phenome-wide consequences. By re-analyzing large data sets already at our disposal, we will be able to
identify novel genes and variants responsible for the telomere shortening and provide a more complete picture
of the role of aberrant telomere length and dysfunctional telomere maintenance in pathophysiological
processes. A better understanding of the genetic and biological drivers of telomere shortening may provide
insights into disease risk, earlier diagnosis, and new kinds of therapies. Our Aims are to: 1) Determine the
genetic basis of telomere shortening in diverse tissues, 2) Determine the phenome-wide consequences of
telomere length using large-scale biobanks, 3) Identify disease causing variants (DVs) in novel genes
associated with Telomere Biology Disorders (TBD)

## Key facts

- **NIH application ID:** 11170170
- **Project number:** 1R56AG089926-01
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** JOY D COGAN
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $430,101
- **Award type:** 1
- **Project period:** 2024-09-15 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11170170

## Citation

> US National Institutes of Health, RePORTER application 11170170, Genomic Basis of Telomere Length Regulation and Consequences for Complex Traits (1R56AG089926-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11170170. Licensed CC0.

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