Association between Leukocyte Telomere Length and Atrial Fibrillation: A Mendelian Randomization Study

Atrial fibrillation (AF) is the most common cardiac arrhythmia worldwide. The prevalence of AF increases significantly associated with increasing age, ranging from less than 0.5% of the population younger than 40 to 5% of those aged 65 and older and more than 10% of those surviving to the eighth decade of life. Therefore, AF is thought to be closely related to biological ageing. Telomeres (TL), repetitive DNA elements located at the ends of chromosomes, have been implicated as potential mediators of biological aging. TL is generally measured in leucocytes due to the easy accessibility of these cells in peripheral blood. Whether a causal effect of leucocytes TL (LTL) on AF is not clear. We used two-sample MR analysis model to evaluate the causal effect of LTL on AF. The summary statistics data for AF and LTL were derived from the recently published largest GWAS. Twenty SNPs at 17 genomic loci were discovered as genetic instruments for LTL. The MR analysis in the fixed-effect inverse-variance weighted models and MR Egger (bootstrap) method showed that LTL was associated with an increased risk of AF (odds ratio [OR], 1.145; 95% CI, 1.065-1.230, P<0.001; OR, 1.158; 95% CI, 1.007-1.331, P=0.021) based on 20 SNPs as the instrument variables. However, the opposite results were observed in other MR methods, which revealed LTL has no strong causal effect on AF at current evidence.