A18709 Mendelian Randomization Study of Causal Relationship of Height on Blood Pressure and Arterial Stiffness

Objectives: Observational studies have shown that greater height is associated with lower systolic blood pressure (SBP) and pulse pressure (PP), and higher diastolic blood pressure (DBP). Height may be a proxy for early life circumstances or other behavioural or psychosocial factors, and thus confound these observations. Genetic variants are unlikely to be affected by confounders and cannot be influenced by reverse causation. We investigated the causal effect of adult height on blood pressure and arterial stiffness using instrumental variable (IV) Mendelian randomization (MR) meta-analysis. Methods: We performed two-sample and multivariable MR analysis using previously published summary statistics of GWAS meta-analysis. Independent SNPs associated with height (primary exposure), BMI and waist circumference were selected. The outcomes were SBP, DBP (N = 317754) and Arterial Stiffness Index (ASI) (N = 109813) from UK-Biobank genome wide analysis. We performed inverse-variance weighted MR (IVW) as main analyses and MR-Egger regression to explore pleiotropy. The analyses were performed on the MR-Base platform. Results: Two sample analyses showed a causal relationship between greater height and lower SBP and higher ASI (figure). Causal effects per standard deviation increase in genetically determined height on SBP (IVW = -0.06 ± 0.01, P = 1.6E-09; MR-Egger = -0.05 ± 0.01, P = 0.04) and ASI (IVW = 0.07 ± 0.01, P = 1.5E-12; MR-Egger = 0.12 ± 0.03, P = 1.2E-06) but not DBP (Egger P value = 0.6). Multivariable MR including BMI and waist circumference as exposures confirmed the causal effect of height on SBP (−0.084 ± 0.02, P = 1.5E-05) and ASI (0.06 (0.09, P = 0.0006) but not DBP. Conclusion: Genetically predicted height is causally associated with higher systolic BP and lower arterial stiffness index with no association with diastolic BP.