ArticleFrontiers in gastroenterology (Lausanne, Switzerland)2026
High-fat diet and portal hypertension: a triangulation approach combining Mendelian randomization with retrospective clinical analysis.
Article in Frontiers in gastroenterology (Lausanne, Switzerland), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Portal hypertension is a major complication of chronic liver disease, but the causal role of dietary factors, particularly high-fat diet, remains unclear due to confounding in observational studies. This study aimed to investigate the relationship between high-fat diet and portal hypertension using a triangulation approach combining Mendelian randomization (MR) and retrospective clinical analysis. Methods: We conducted a two-sample Mendelian randomization analysis using summary-level genome-wide association study (GWAS) data for dietary fat intake (n = 268,922) and portal hypertension-related traits. Eighteen independent SNPs served as genetic instruments (mean F-statistic = 34.2, collectively explaining 2.8% of phenotypic variance). Inverse variance weighted (IVW), weighted median, MR-Egger regression, and mode-based methods were employed. Sensitivity analyses included MR-Egger intercept test, Cochran's Q statistic, MR-PRESSO, and leave-one-out analysis. Additionally, a retrospective cross-sectional clinical study was conducted on 72 patients with portal hypertension who underwent hepatic venous pressure gradient (HVPG) measurement. Results: 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 Conclusion: 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.
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