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This study employed Mendelian randomization (MR) to assess bidirectional causal relationships and explore potential implications for heart failure (HF) risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>A bidirectional two-sample MR analysis was conducted using genome-wide association study (GWAS) summary data from European populations (GERD: 129,080 cases and 473,524 controls; AF\/AFL: 22,068 cases and 116,926 controls; Obesity: 4793 cases and 209,884 controls). Genetic instruments were selected for GERD and AF\/AFL, with inverse variance weighting (IVW) as the primary analytical method to examine causality. Multivariable MR (MVMR) adjusted for obesity was performed to assess direct causal effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>IVW analysis demonstrated a significant causal effect of GERD on AF\/AFL risk (OR = 1.373, 95% CI = 1.208\u20131.600, P = 0.017), which persisted after MVMR adjustment for obesity (OR = 1.303, 95% CI = 1.127\u20131.507, P &amp;lt; 0.001). Two-way analysis indicated no reverse causality. Sensitivity analyses supported result robustness with minimal pleiotropy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Genetic liability to GERD independently increases AF\/AFL risk, unaffected by obesity pathways. Considering the well-established role of AF\/AFL in the pathogenesis and progression of HF, our findings position GERD as a potential modifiable target within the causal pathway. Identification and management of GERD may therefore contribute to reducing atrial arrhythmia burden and subsequent HF risk.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ehf2.70009","type":"journal-article","created":{"date-parts":[[2025,11,9]],"date-time":"2025-11-09T15:09:38Z","timestamp":1762700978000},"page":"4401-4409","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Gastroesophageal Reflux Disease and Risk of Atrial Fibrillation\/Flutter: Implications for Heart Failure Progression"],"prefix":"10.1093","volume":"12","author":[{"given":"Wansong","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University , Nanchang ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingxing","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of 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