Abstract
This study aimed to dissect the direct effect of smoking and its indirect effect through body mass index (BMI) on leukocyte telomere length (LTL) and to distinguish the mediation and suppression effects of BMI. The study cohort included 1,037 adults (729 Whites and 308 African Americans; 42.1% males; mean age: 40.3 years) with LTL measurements by Southern blotting. General third variable models were used to distinguish the mediation and suppression effects of BMI on the smoking-LTL association. After adjusting for age, race, sex and alcohol drinking, the total effect of smoking on LTL was significant (standardized regression coefficient, β= -0.061, p=0.034) without BMI included in the model. With additional adjustment for BMI, the indirect effect of smoking on LTL through BMI was estimated at β= 0.011 (p=0.023), and the direct effect of smoking on LTL was strengthened to β= -0.072 (p=0.012). The results were similar when pack-years of smoking was used. The effect parameters did not differ significantly between race and sex groups. These results suggest that BMI has a suppression effect, not a mediation effect, on the smoking-LTL association, which potentially contributes to previous inconsistencies in the effect of smoking on LTL.