An investigation of genetically determined telomere length and its impact on disease in UK Biobank

Telomere length has been proposed as a marker of biological age, and numerous studies have shown associations between directly measured telomere length and age-related disease risk. The study into underlying genetic contribution to telomere length have recently begun to emerge and bring an understanding of the genetic effect of telomere length on human health.

This study investigates genetically determined telomere length and its association with age-related diseases. A genetic risk score was built within UK Biobank for each participant using the genetic determinants of telomere length identified in our large-scale genome-wide meta-analysis study and tested against a curated list of 127 diseases. Some of these associations were confirmed as causal using mendelian randomisation and taken further to model the effects on time to disease onset using survival analysis.

Shorter genetically determined telomere length was causally associated with an increased risk of cardiovascular, endocrine, and immune disease phenotypes, and a decreased risk of diseases with high proliferative capacity. This study provides evidence that genetically determined telomere length is involved in the aetiology of age-related disease and influences time to disease onset, which highlights the primary function of telomere length in limiting cell division. A genetic predisposition to shorter telomere length may contribute to an accelerated loss of telomeric repeats during cell division. Whilst a genetic predisposition to longer telomere length may contribute to increased telomere length maintenance that accumulates mutations that may lead to malignancies.