Telomere length and common disease: study design and analytical challenges

Hum Genet. 2015 Jul;134(7):679-89. doi: 10.1007/s00439-015-1563-4. Epub 2015 May 19.


Telomeres, the repetitive sequences that protect the ends of chromosomes, help to maintain genomic integrity and are of key importance to human health. The aim here is to give an overview of the evidence for the importance of telomere length (TL) to the risk of common disease, considering the strengths and weaknesses of different epidemiological study designs. Methods for measuring TL are described, all of which are subject to considerable measurement error. TL declines with age and varies in relation to factors such as smoking and obesity. It is also highly heritable (estimated heritability of ~40 to 50%), and genome-wide studies have identified a number of associated genetic variants. Epidemiological studies have shown shorter TL to be associated with risk of a number of common diseases, including cardiovascular disease and some cancers. The relationship with cancer appears complex, in that longer telomeres are associated with higher risk of some cancers. Prospective studies of the relationship between TL and disease, where TL is measured before diagnosis, have numerous advantages over retrospective studies, since they avoid the problems of reverse causality and differences in sample handling, but they are still subject to potential confounding. Studies of the genetic predictors of TL in relation to disease risk avoid these drawbacks, although they are not without limitations. Telomere biology is of major importance to the risk of common disease, but the complexities of the relationship are only now beginning to be understood.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cardiovascular Diseases / genetics
  • Cardiovascular Diseases / metabolism*
  • Humans
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Obesity / genetics
  • Obesity / metabolism*
  • Risk Factors
  • Smoking / genetics
  • Smoking / metabolism*
  • Telomere / genetics
  • Telomere / metabolism*
  • Telomere Homeostasis*