{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T04:58:46Z","timestamp":1790657926351,"version":"4.1.0"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003819","name":"Natural Science Foundation of Hubei Province","doi-asserted-by":"publisher","award":["No. 2024AFD338"],"award-info":[{"award-number":["No. 2024AFD338"]}],"id":[{"id":"10.13039\/501100003819","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Gastroenterol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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\u2019s 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      MR analysis provided evidence consistent with a causal association between genetically predicted high-fat diet and increased risk of portal hypertension (IVW OR\u00a0=\u00a01.28 per SD increase, 95% CI: 1.15\u20131.42, p = 1.0 \u00d7 10\n                      <jats:sup>-5<\/jats:sup>\n                      ). Results were consistent across multiple MR methods. Sensitivity analyses showed no evidence of directional pleiotropy (MR-Egger intercept p = 0.178), significant heterogeneity (Cochran\u2019s 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 &amp;lt; 0.001), and this association remained significant after multivariate adjustment (\u03b2 = 0.85, 95% CI: 0.52\u20131.18, p &amp;lt; 0.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats: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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fgstr.2026.1927449","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T04:40:27Z","timestamp":1790656827000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["High-fat diet and portal hypertension: a triangulation approach combining Mendelian randomization with retrospective clinical analysis"],"prefix":"10.3389","volume":"5","author":[{"given":"Yu","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Organ Transplantation, Renmin Hospital of Wuhan University","place":["Wuhan, Hubei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siqi","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of 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