Observational and genetic analyses of the bidirectional relationship between depression and hypertension

While the association between depression and hypertension has been extensively investigated, the pattern and nature of such association remain inconclusive. We sought to investigate the bidirectional relationship between depression and hypertension and its causal. We first performed observational analyses using longitudinal data from the UK Biobank. We then performed genetic analyses leveraging summary statistics from large-scale genome-wide association studies (GWASs) conducted in European ancestry for depression and hypertension. Observational analysis suggested a significant bidirectional phenotypic association between depression and hypertension (Depression → Hypertension: HR = 1.27, 95 % CI: 1.19, 1.36; Hypertension → Depression: HR = 1.65, 95 % CI: 1.58, 1.72). Linkage disequilibrium score regression demonstrated a positive genetic correlation between the two conditions (r =0.15, P = 5.75 × 10 ). Bidirectional two-sample Mendelian randomization (MR) suggested that genetic liability to depression was significantly associated with an increased risk of hypertension (OR = 1.27, 95 % CI: 1.12, 1.43), while the genetic liability to hypertension was not associated with the risk of depression (OR = 1.01, 95 % CI: 0.99, 1.03). Multivariate MR, after adjusting for smoking, drinking, and body mass index, further supported an independent causal effect of genetic liability to depression on hypertension risk (OR = 1.10, 95 % CI: 1.02, 1.18). (1) interference of confounders, (2) absence of adequate statistical power, and (3) limitation to European populations. Our study indicates depression is a causal risk factor for hypertension, whereas the reverse maybe not. Findings support that prevention of depression might help in decreasing hypertension incidence.