Data Sheet 1_High-fat diet and portal hypertension: a triangulation approach combining Mendelian randomization with retrospective clinical analysis.docx

Additionally, a retrospective cross-sectional clinical study was conducted on 72 patients with portal hypertension who underwent hepatic venous pressure gradient (HVPG) measurement.</p>Results<p>MR analysis provided evidence consistent with a causal association between genetically predicted high-fat diet and increased risk of portal hypertension (IVW OR = 1.28 per SD increase, 95% CI: 1.15–1.42, p = 1.0 × 10^-5).

Results were consistent across multiple MR methods. Sensitivity analyses showed no evidence of directional pleiotropy (MR-Egger intercept p = 0.178), significant heterogeneity (Cochran’s Q p = 0.241), or MR-PRESSO-detected outliers (global test p = 0.312). In the clinical cohort, high-fat diet score was positively correlated with HVPG (r = 0.700, p < 0.001), and this association remained significant after multivariate adjustment (β = 0.85, 95% CI: 0.52–1.18, p < 0.001).</p>Conclusion<p>Using a triangulation approach, we found consistent evidence from both Mendelian randomization and retrospective clinical analysis that a high-fat diet is linked to increased portal pressure.

These complementary findings strengthen the overall evidence base and highlight the potential importance of dietary fat modification in portal hypertension management.</p>