Metabolic dysfunction-associated steatotic liver disease and gastroesophageal reflux disease: a mendelian randomization study in European and East Asian populations
BackgroundNumerous observational studies have shown a potential association between metabolic dysfunction-associated steatotic liver disease (MASLD) and gastroesophageal reflux disease (GERD). However, causality is unclear. This study utilized genome-wide association study (GWAS) genetic data to exp...
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Frontiers Media S.A.
2024-12-01
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| author | Chen’guang Su Zheng Liao Hewen Li Yinxuan Pei Zixiang Wang Jian Li Jinlong Liu Jinlong Liu |
| author_facet | Chen’guang Su Zheng Liao Hewen Li Yinxuan Pei Zixiang Wang Jian Li Jinlong Liu Jinlong Liu |
| author_sort | Chen’guang Su |
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| description | BackgroundNumerous observational studies have shown a potential association between metabolic dysfunction-associated steatotic liver disease (MASLD) and gastroesophageal reflux disease (GERD). However, causality is unclear. This study utilized genome-wide association study (GWAS) genetic data to explore the causal relationship between MASLD and GERD in European and East Asian populations.MethodsThis study utilized a bidirectional, two-sample Mendelian randomization (MR) approach. All disease data were obtained from the GWAS database, and single nucleotide polymorphisms strongly associated with exposure were selected as instrumental variables. The inverse variance weighted (IVW) method is primarily utilized to evaluate the causal relationship between exposure and outcome. Finally, sensitivity analyses were performed to ensure the robustness of the results.ResultsThe IVW estimates indicated that non-alcoholic fatty liver disease (NAFLD) (odds ratio (OR) = 1.054, 95% confidence interval (CI), 0.966–1.150, p = 0.236) and percent liver fat (OR = 0.977, 95% CI, 0.937–1.018, p = 0.258) in European population were not linked to a higher risk of GERD. However, GERD in European population was associated with an increased risk of NAFLD (OR = 1.485, 95% CI, 1.274–1.729, p < 0.001) and percent liver fat (OR = 1.244, 95% CI, 1.171–1.321, p < 0.001). In addition, the IVW analysis in East Asian population showed that alanine aminotransferase (ALT) was associated with an increased risk of GERD (OR = 2.305, 95% CI, 1.241–4.281, p = 0.008), whereas aspartate aminotransferase (AST) had no causal effects on GERD risk (OR = 0.973, 95% CI, 0.541–1.749, p = 0.926). Furthermore, the associations between GERD and ALT (OR = 1.007, 95% CI, 0.998–1.015, p = 0.123) or AST (OR = 1.004, 95% CI, 0.997–1.012, p = 0.246) were not significant. After removing outliers, a significant correlation between GERD and ALT was observed (OR = 1.009, 95% CI, 1.001–1.016, p = 0.020).ConclusionThere was reverse causality between MASLD and GERD in European population, while there was bidirectional causality between a proxie for MASLD (ALT) and GERD in East Asian population. This study can provide novel insights into cross-ethnic genetic research on MASLD and GERD. |
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| institution | Kabale University |
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| spelling | doaj-art-c771633b6a574256a8d7fc2c1f88e0822024-12-05T06:28:48ZengFrontiers Media S.A.Frontiers in Genetics1664-80212024-12-011510.3389/fgene.2024.14283341428334Metabolic dysfunction-associated steatotic liver disease and gastroesophageal reflux disease: a mendelian randomization study in European and East Asian populationsChen’guang Su0Zheng Liao1Hewen Li2Yinxuan Pei3Zixiang Wang4Jian Li5Jinlong Liu6Jinlong Liu7Department of Hepatobiliary Surgery, Affiliated Hospital of Chengde Medical University, Chengde, Hebei, ChinaDepartment of Hepatobiliary Surgery, Affiliated Hospital of Chengde Medical University, Chengde, Hebei, ChinaDepartment of Minimally Invasive Spine Surgery, Affiliated Hospital of Chengde Medical University, Chengde, Hebei, ChinaDepartment of Hepatobiliary Surgery, Affiliated Hospital of Chengde Medical University, Chengde, Hebei, ChinaDepartment of Hepatobiliary Surgery, Affiliated Hospital of Chengde Medical University, Chengde, Hebei, ChinaDepartment of Hepatobiliary Surgery, Affiliated Hospital of Chengde Medical University, Chengde, Hebei, ChinaDepartment of Hepatobiliary Surgery, Affiliated Hospital of Chengde Medical University, Chengde, Hebei, ChinaHebei Key Laboratory of Panvascular Diseases, Chengde, Hebei, ChinaBackgroundNumerous observational studies have shown a potential association between metabolic dysfunction-associated steatotic liver disease (MASLD) and gastroesophageal reflux disease (GERD). However, causality is unclear. This study utilized genome-wide association study (GWAS) genetic data to explore the causal relationship between MASLD and GERD in European and East Asian populations.MethodsThis study utilized a bidirectional, two-sample Mendelian randomization (MR) approach. All disease data were obtained from the GWAS database, and single nucleotide polymorphisms strongly associated with exposure were selected as instrumental variables. The inverse variance weighted (IVW) method is primarily utilized to evaluate the causal relationship between exposure and outcome. Finally, sensitivity analyses were performed to ensure the robustness of the results.ResultsThe IVW estimates indicated that non-alcoholic fatty liver disease (NAFLD) (odds ratio (OR) = 1.054, 95% confidence interval (CI), 0.966–1.150, p = 0.236) and percent liver fat (OR = 0.977, 95% CI, 0.937–1.018, p = 0.258) in European population were not linked to a higher risk of GERD. However, GERD in European population was associated with an increased risk of NAFLD (OR = 1.485, 95% CI, 1.274–1.729, p < 0.001) and percent liver fat (OR = 1.244, 95% CI, 1.171–1.321, p < 0.001). In addition, the IVW analysis in East Asian population showed that alanine aminotransferase (ALT) was associated with an increased risk of GERD (OR = 2.305, 95% CI, 1.241–4.281, p = 0.008), whereas aspartate aminotransferase (AST) had no causal effects on GERD risk (OR = 0.973, 95% CI, 0.541–1.749, p = 0.926). Furthermore, the associations between GERD and ALT (OR = 1.007, 95% CI, 0.998–1.015, p = 0.123) or AST (OR = 1.004, 95% CI, 0.997–1.012, p = 0.246) were not significant. After removing outliers, a significant correlation between GERD and ALT was observed (OR = 1.009, 95% CI, 1.001–1.016, p = 0.020).ConclusionThere was reverse causality between MASLD and GERD in European population, while there was bidirectional causality between a proxie for MASLD (ALT) and GERD in East Asian population. This study can provide novel insights into cross-ethnic genetic research on MASLD and GERD.https://www.frontiersin.org/articles/10.3389/fgene.2024.1428334/fullmetabolic dysfunction-associated steatotic liver diseasegastroesophageal reflux diseasemendelian randomizationcausal effectgenome-wide association studies |
| spellingShingle | Chen’guang Su Zheng Liao Hewen Li Yinxuan Pei Zixiang Wang Jian Li Jinlong Liu Jinlong Liu Metabolic dysfunction-associated steatotic liver disease and gastroesophageal reflux disease: a mendelian randomization study in European and East Asian populations Frontiers in Genetics metabolic dysfunction-associated steatotic liver disease gastroesophageal reflux disease mendelian randomization causal effect genome-wide association studies |
| title | Metabolic dysfunction-associated steatotic liver disease and gastroesophageal reflux disease: a mendelian randomization study in European and East Asian populations |
| title_full | Metabolic dysfunction-associated steatotic liver disease and gastroesophageal reflux disease: a mendelian randomization study in European and East Asian populations |
| title_fullStr | Metabolic dysfunction-associated steatotic liver disease and gastroesophageal reflux disease: a mendelian randomization study in European and East Asian populations |
| title_full_unstemmed | Metabolic dysfunction-associated steatotic liver disease and gastroesophageal reflux disease: a mendelian randomization study in European and East Asian populations |
| title_short | Metabolic dysfunction-associated steatotic liver disease and gastroesophageal reflux disease: a mendelian randomization study in European and East Asian populations |
| title_sort | metabolic dysfunction associated steatotic liver disease and gastroesophageal reflux disease a mendelian randomization study in european and east asian populations |
| topic | metabolic dysfunction-associated steatotic liver disease gastroesophageal reflux disease mendelian randomization causal effect genome-wide association studies |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2024.1428334/full |
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