Modifiable traits, healthy behaviours, and leucocyte telomere length

Abstract

Background: Telomere length is associated with risk of several age-related diseases and cancers. The extent to which telomere length may be modifiable through lifestyle and behaviour and whether this has any clinical consequences is unknown. Methods: In up to 422,797 participants in UK Biobank, we investigated associations of leucocyte telomere length (LTL) with 117 potentially modifiable traits, as well as two indices of healthy behaviours incorporating smoking, physical activity, diet, maintenance of a healthy body weight and alcohol intake. Associations were interpreted as age-related change in LTL by dividing the trait beta coefficients with the age-coefficient. We used Mendelian Randomisation (MR) to test causality of the observed associations of educational attainment and smoking behaviour with LTL. We investigated whether the associations of LTL with 22 diseases were modified by the number of healthy behaviours and the extent to which the associations of more healthy behaviours with greater life expectancy and lower risk of coronary artery disease (CAD) may be mediated through LTL. Results: 71 traits showed significant associations with LTL but most were modest, equivalent to <1 year of age-related change in LTL. In multivariable analyses of 17 traits with stronger associations (equivalent to ≥2 years of age-related change in LTL), five traits (oily fish intake, educational attainment, general health status, walking pace and current smoking) remained significant. MR analysis suggested that educational attainment and smoking behaviour causally affect LTL. Both indices of healthy behaviour were positively and linearly associated with LTL, with those with the healthiest behaviour having longer LTL equivalent to approx. 3.5 years of age-related change in LTL when compared with those with the least heathy behaviours (P<0.001). However, healthy behaviours only explained <0.2% of the total variation in LTL and did not significantly modify the association of LTL with risk of any of the diseases studied. Neither the association of more healthy behaviours on greater life expectancy or lower risk of CAD were substantially mediated through LTL. Conclusions: Several potentially modifiable traits and healthy behaviours have a quantifiable association with LTL, at least some of which are likely to be causal. However, these effects are not of a sufficient magnitude to substantially alter the association between LTL and various diseases or life expectancy.