Genetic relationship between ageing and coronary heart disease: a Mendelian randomization study.

Abstract

Genetic relationship between ageing and coronary heart disease has not been well investigated. The aim of the study was to explore the association of several ageing biomarkers with the risk of several types of coronary heart disease using the Mendelian randomization approach. Summary data for telomere length, four epigenetic clocks (such as intrinsic epigenetic age acceleration), four types of coronary heart disease (such as myocardial infarction) were collected from the most updated and available genome-wide association studies. Instrumental variables were extracted from the exposure-related summary data according to correlation, independence and exclusivity assumptions. Three Mendelian randomization methods (such as inverse variance weighted) were used for causal inference. Four sensitivity analyses (such as MR-Egger intercept) were performed to prevent horizontal pleiotropy. Inverse variance weighted reported that longer telomere length was related to the lower risk of myocardial infarction, angina pectoris, unstable angina pectoris and coronary atherosclerosis (P = 8.840e-11, P = 9.830e-04, P = 1.539e-05, P = 2.607e-09). Inverse variance weighted also reported that four epigenetic clocks might be not implicated in the risk of these coronary heart diseases. Furthermore, there was not enough evidence to confirm the effect of coronary heart disease on these ageing biomarkers. Longer telomere length, but not the epigenetic clock changes, genetically decreased the risk of coronary heart disease. Considering that telomere length and epigenetic clocks were two independent ageing biomarkers, the correlation between ageing and coronary heart disease might be redefined at the genetic level.