The role of glycaemic, lipid, blood pressure and obesity risk factors as mediators of the effect of height on Coronary Artery Disease and Type 2 Diabetes Mellitus: A Mendelian Randomisation Study

We investigated by Mendelian Randomisation (MR) analyses the causal effect of adult height on coronary artery disease (CAD) (23,755 cases, 425,339 controls) and type 2 diabetes (T2D) (29,427 cases, 416,908 controls) in UK Biobank. We then examined whether such effects are mediated via known cardiometabolic risk factors including body mass index (BMI), glycaemic traits, lipid levels and blood pressure. We further cross-checked our findings by two-sample MR and Multivariate MR analyses with publicly available summary statistics data. One standard deviation (SD) higher genetically determined height (~6.5 cm) was causally associated with a 14% decrease in CAD risk (OR= 0.86, 95% CI= 0.790.94). This causal association remained significant after performing sensitivity analyses relaxing pleiotropy assumptions. The causal effect of height on CAD risk appeared to be independent of risk factors such as lipid levels, blood pressure and BMI; association was reduced by only 1-3% after adjustment for potential mediators. We observed no direct causal effect of height on T2D risk, once its effect on BMI was taken into account (OR= 0.99, 95% CI= 0.96-1.02), suggesting that BMI acts as a mediator.