Exploring the Causal Relationships Between Anxiety, Obesity, and Hypertension: A Two-Sample Mendelian Randomization Study.

Background: Both anxiety and obesity have been implicated in hypertension development, with emerging evidence suggesting metabolic risk factors as potential mediators. Notably, obesity may partially mediate the link between anxiety and hypertension. However, the causal relationships among these factors remain unclear. To address this, we conducted a two-sample Mendelian randomization (MR) analysis to elucidate their causal relationship.

Methods: We conducted a two-sample MR analysis using genome-wide association study (GWAS) summary statistics from European ancestry cohorts. The inverse-variance weighted (IVW) method was used as the primary analytical approach, with sensitivity analyses and heterogeneity tests conducted to ensure robustness. Additionally, a two-step MR approach was conducted to quantify the proportion of the anxiety-hypertension association mediated through obesity-related pathways.

Results: The two-sample MR analysis demonstrated significant causal effects of anxiety (OR=1.025, 95% CI 1.011-1.038; P<0.001) and obesity (OR=1.010, 95% CI 1.007-1.013; P<0.001) on hypertension risk. Bidirectional analysis revealed a unidirectional causal association between anxiety and obesity (OR=1.518, 95% CI 1.044-2.206; P=0.029), with no evidence of reverse causation from obesity to anxiety (OR=1.014, 95% CI 0.990-1.039; P=0.268). Mediation analysis estimated that 17.4% (95% CI 5.3-29.5%) of anxiety's total effect on hypertension risk was mediated through adiposity-related pathways.

Conclusion: The two-sample MR analysis in this study confirmed a causal relationship between anxiety and hypertension. Obesity was found to partially mediate this association. Our causal estimates support weight management interventions as an effective psychosomatic strategy for preventing hypertension in individuals with anxiety, particularly due to the modifiable nature of obesity-related risk factors.