Background: Recently, several observational studies reported that smoking is associated with shortened leucocyte telomere length (LTL), which has been considered as a marker of tissue self-repair capability, regeneration and aging. However, patterns of tobacco consumption and cessation varied, whether concrete smoking status and quantity are the causes for shortened LTL remains unknown.
 
Method: Genetic summary statistics of smoking status (current smoker, never smoking, previous smoker), smoking quantity (pack years of cigarette consumption) as well as LTL were sourced from the UK Biobank. Two-sample mendelian randomization (MR) method was adopted, while allele harmonization and clumping were performed in advance. MR estimates of inverse variance weighted method were obtained, and R 4.2.2 was used for all analyses.
 
Results: There were 472,174 eligible European ancestry participants, and 113 instrumental SNPs regarding smoking status (current: 15 SNPs; never: 78 SNPs; previous: 20 SNPs) as well as 11 SNPs regarding pack years of cigarette smoking included. For the relationships, current smoking status was statistical significantly associated with shorter LTL (r=-0.27, p=0.013), whereas never smoking was positively associated with LTL (r=0.21, p<0.0001). Former cigarette smoking failed to reach significance though a negative trend presented (r=-0.15, p=0.221). In terms of consumption quantity, larger pack years was significantly linked to shorter LTL (r=-0.08, p=0.008).
 
Conclusion: This MR study supports a causal effect of smoking on risk of shortened LTL. Smoking may inhibit tissue repair and regeneration while quitting may considerably decrease related risk.