Assessing Gene-Environment Interaction in the Association Between Smoking and Leukocyte Telomere Length

Abstract

Telomere length is influenced by both genetic and environmental factors, including smoking behavior. While smoking is associated with shorter telomeres, this association may vary by genotype. In a subset of the UK Biobank cohort (N = 360,909) with genetically inferred European ancestry, we analyzed 581,069 common single nucleotide polymorphisms (SNPs) and average relative telomere length estimates derived from quantitative PCR (qPCR) to test whether the association between ever/never smoking status and telomere length differs by genotype. One SNP, rs4418881, reached genome-wide significance (P = 4.49e-8) in the 2 degrees of freedom gene-environment interaction joint test but did not reach significance in the overall genome-wide association study (P = 4.19e-7). Stratified analyses revealed that rs4418881 was genome-wide significant in ever smokers (P = 1.06e-8) but not in never smokers (P = 0.35), suggesting that this SNP may modify the effect of smoking on telomere length.