# Identifying potentially modifiable exposures to improve telomere health and disease outcomes

> **NIH NIH R21** · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · 2020 · $247,929

## Abstract

Project Summary/Abstract
Telomeres are non-coding sequences at the end of chromosomes that shorten with each cell division as we
age. Telomere length (TL) may be a global biomarker of health, as shorter telomere length is associated with
poor survival, age-related diseases/conditions, and some cancers. Both genetic and non-genetic factors
influence telomere length and the underlying mechanisms remain unclear. We propose to use UK Biobank
data to delineate modifiable exposures that directly influence or moderate telomere length, and how the
relationships influence health and risk of disease (responding to PA-19-073). UK Biobank offers an
exceptionally large sample size (over 500,000 participants), with telomere length measures, genetic and
phenotypic data. Most notably, it provides multidimensional data on exposures, covering early life, socio-
economic factors, environmental exposures, psychologically traumatic events, plus lifestyle and behavioral
factors, including accelerometer measures of physical activity. We hypothesize that identifying and
characterizing behavioral and environmental factors associated with telomere length, especially in older
groups, will inform future efforts to therapeutically target telomeres through personalized, non-pharmacological
interventions. We also hypothesize that a better understanding of gene-environment interactions will support
the use of telomere length measurement for monitoring individual health status, to alert health providers to the
need for preventive and early health care, ultimately improving health outcomes. We aim to conduct an
environment-wide association study (EWAS) to identify novel exposures and gene-environment interactions on
telomere length. We also will examine the intermediate role of telomere length in the relationships between
exposures and disease outcomes. Additionally, we aim to strengthen our EWAS by inherited genetic variants
associated with exposures and telomere length, to investigate bidirectional exposure and TL causal
relationships. As inherited genetic variants are unchanging during life, they can be used to conduct pseudo
randomized trials to produce more robust associations to confounding and reverse causation. Our team is
multidisciplinary, with expertise in statistical genetics, genetic epidemiology, bioinformatics, clinical geriatrics,
and physical activity epidemiology. The team has already produced several leading outputs using UK Biobank
data, including a study on telomere length and aging-related outcomes via genetic variants associated with
telomere length. We request funding to extend this work to identify novel modifiable exposures influencing
telomere length, and establish the path from modifiable exposures to telomere length and then health-related
outcomes. Our findings will be useful to prioritize modifiable exposures for personalized interventions with the
ultimate goal of improving telomere health and disease outcomes. In the future, we will seek to replic...

## Key facts

- **NIH application ID:** 10057808
- **Project number:** 1R21NR018963-01A1
- **Recipient organization:** UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
- **Principal Investigator:** Chia-Ling Kuo
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $247,929
- **Award type:** 1
- **Project period:** 2020-09-02 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10057808

## Citation

> US National Institutes of Health, RePORTER application 10057808, Identifying potentially modifiable exposures to improve telomere health and disease outcomes (1R21NR018963-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10057808. Licensed CC0.

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