Leukocyte Telomere Length and Cardiac Structure and Function: A Mendelian Randomization Study

Abstract

AbstractExisting research demonstrates association of shorter telomere length (TL) with increased risk of agerelated health outcomes including cardiovascular diseases. However, the direct causality of these relationships is not definitively established. Cardiovascular aging at an organ-level may be captured using image derived phenotypes (IDPs) of cardiac anatomy and function. In the current study, we use two-sample Mendelian Randomization (MR) to assess the causal link between TL and 54 cardiac magnetic resonance imaging (CMR) measures representing structure and function across the four cardiac chambers. Genetically predicted shorter TL was causally linked to smaller ventricular cavity sizes including left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV), lower left ventricular mass (LVM) and pulmonary artery. The association with LVM (β= 0.217, PFDR= 0.016) remained significant after multiple testing adjustment, whilst other associations were attenuated. Our findings support a causal role for shorter TL and faster cardiac aging, with the most prominent relationship with LVM.