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Peer-reviewedCC BYGastroenterology research and practice

Mendelian Randomization-Based Analysis of Causal Effects Between Statins and Common Upper Gastrointestinal Diseases.

  • Wenchu Zhao1
  • Jiejun Hou2
  • Jinyi Chen1
  • Jinhua Pang1
  1. 1Shaanxi University of Chinese Medicine Xianyang China sntcm.edu.cn.
  2. 2Shaanxi University of Traditional Chinese Medicine Hospital Xianyang China.
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Abstract

Background

Statins are widely used for cardiovascular disease prevention and exhibit multiple pleiotropic effects, including anti-inflammatory properties. However, conclusions from observational studies regarding the causal relationship between statin use and upper gastrointestinal diseases (such as gastric cancer, gastric ulcer, and functional dyspepsia) remain controversial. This study is aimed at systematically evaluating the causal association between statin-targeted gene (HMGCR)-mediated reductions in low-density lipoprotein cholesterol (LDL-C) levels and common upper gastrointestinal diseases using drug-targeted Mendelian randomization (MR). This approach seeks to uncover potential unintended effects.Methods

We extracted genetic variants associated with the HMGCR gene region from genome-wide association studies (GWAS) as instrumental variables to simulate the lipid-lowering effects of statins. Outcome data were derived from large-scale GWAS meta-analyses covering gastric cancer (n = 202,308), gastroenteritis (n = 7651), gastric ulcer (n = 361,194), gastroesophageal reflux disease (n = 462,933), and functional dyspepsia (n = 84,572). The primary analysis employed inverse variance weighting (IVW), with sensitivity assessments for heterogeneity and pleiotropy conducted via MR-Egger, weighted median, and MR-PRESSO methods.Results

Genetically predicted HMGCR-mediated LDL-C reduction was associated with reduced risk of gastric cancer (OR = 0.588, 95% CI: 0.423-0.816, p = 0.002), gastroenteritis (OR = 0.257, 95% CI: 0.086-0.766, p = 0.015), and gastric ulcer (OR = 0.996, 95% CI: 0.993-0.998, p = 0.003). However, analysis indicated a potential increased risk of functional dyspepsia (OR = 1.437, 95% CI: 1.014-2.036, p = 0.042). No significant causal association was found between statin use and gastroesophageal reflux disease (OR = 0.999, 95% CI: 0.992-1.006, p = 0.773). Sensitivity analyses confirmed the robustness of the results, with no evidence of significant level-specific multiplicity.Conclusion

This study provides genetic evidence supporting the potential protective effects of statins against gastric cancer, gastritis, and gastric ulcers, which may be associated with their anti-inflammatory properties. However, the potential increased risk of functional dyspepsia suggests the complexity of the drug's effects. These findings provide scientific basis for the repositioning of statins in gastrointestinal diseases and their safety assessment.

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Cite

BibTeXRIS
BibTeX
@article{zhao2026mendelian,
  title = {{Mendelian Randomization-Based Analysis of Causal Effects Between Statins and Common Upper Gastrointestinal Diseases.}},
  author = {Wenchu Zhao and Jiejun Hou and Jinyi Chen and Jinhua Pang},
  journal = {Gastroenterology research and practice},
  year = {2026},
  month = oct,
  doi = {10.1155/grp/5335710},
  url = {https://europepmc.org/article/MED/42959810},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Mendelian Randomization-Based Analysis of Causal Effects Between Statins and Common Upper Gastrointestinal Diseases.
AU  - Wenchu Zhao
AU  - Jiejun Hou
AU  - Jinyi Chen
AU  - Jinhua Pang
PY  - 2026
DA  - 2026/10/29
JO  - Gastroenterology research and practice
DO  - 10.1155/grp/5335710
UR  - https://europepmc.org/article/MED/42959810
AB  - Background  Statins are widely used for cardiovascular disease prevention and exhibit multiple pleiotropic effects, including anti-inflammatory properties. However, conclusions from observational studies regarding the causal relationship between statin use and upper gastrointestinal diseases (such as gastric cancer, gastric ulcer, and functional dyspepsia) remain controversial. This study is aimed at systematically evaluating the causal association between statin-targeted gene (HMGCR)-mediated reductions in low-density lipoprotein cholesterol (LDL-C) levels and common upper gastrointestinal diseases using drug-targeted Mendelian randomization (MR). This approach seeks to uncover potential unintended effects.Methods  We extracted genetic variants associated with the HMGCR gene region from genome-wide association studies (GWAS) as instrumental variables to simulate the lipid-lowering effects of statins. Outcome data were derived from large-scale GWAS meta-analyses covering gastric cancer (n = 202,308), gastroenteritis (n = 7651), gastric ulcer (n = 361,194), gastroesophageal reflux disease (n = 462,933), and functional dyspepsia (n = 84,572). The primary analysis employed inverse variance weighting (IVW), with sensitivity assessments for heterogeneity and pleiotropy conducted via MR-Egger, weighted median, and MR-PRESSO methods.Results  Genetically predicted HMGCR-mediated LDL-C reduction was associated with reduced risk of gastric cancer (OR = 0.588, 95% CI: 0.423-0.816, p = 0.002), gastroenteritis (OR = 0.257, 95% CI: 0.086-0.766, p = 0.015), and gastric ulcer (OR = 0.996, 95% CI: 0.993-0.998, p = 0.003). However, analysis indicated a potential increased risk of functional dyspepsia (OR = 1.437, 95% CI: 1.014-2.036, p = 0.042). No significant causal association was found between statin use and gastroesophageal reflux disease (OR = 0.999, 95% CI: 0.992-1.006, p = 0.773). Sensitivity analyses confirmed the robustness of the results, with no evidence of significant level-specific multiplicity.Conclusion  This study provides genetic evidence supporting the potential protective effects of statins against gastric cancer, gastritis, and gastric ulcers, which may be associated with their anti-inflammatory properties. However, the potential increased risk of functional dyspepsia suggests the complexity of the drug's effects. These findings provide scientific basis for the repositioning of statins in gastrointestinal diseases and their safety assessment.
SN  - 1687-6121
SN  - 1687-630X
ER  -