Assessing causality between osteoarthritis and gastrointestinal disorders: a Mendelian randomization study
Huiqing Xu1, Jiahe Wei1, Dingwan Chen1
1School of Public Health, Hangzhou Medical College, Hangzhou, China.
Scientific Reports
|November 10, 2023
Summary
Osteoarthritis (OA) increases the risk of gastroesophageal reflux disease (GORD), partly due to opioid use, but not non-steroidal anti-inflammatory drugs (NSAIDs). Gastrointestinal disorders do not causally affect OA.
Area of Science:
- Genetics and Epidemiology
- Gastroenterology
- Rheumatology
Background:
- Observational studies suggest a link between osteoarthritis (OA) and gastrointestinal (GI) disorders, but causality remains unclear.
- Investigating causal relationships is crucial for understanding disease pathogenesis and informing treatment strategies.
Purpose of the Study:
- To assess the bidirectional causal association between osteoarthritis (OA) and specific GI diseases: peptic ulcer disease (PUD), gastroesophageal reflux disease (GORD), and inflammatory bowel disease (IBD).
- To explore the potential mediating roles of non-steroidal anti-inflammatory drugs (NSAIDs) and opioid use in the OA-GI disorder relationship using two-step Mendelian randomization (TSMR).
- To validate findings using multivariable Mendelian randomization (MVMR) analysis, considering prescription history.
Main Methods:
- Bidirectional Mendelian randomization (MR) analysis utilizing genome-wide association studies (GWAS) data.
- Two-step MR (TSMR) to investigate mediating effects of NSAIDs and opioids.
- Multivariable MR (MVMR) to adjust for prescription history.
Main Results:
- Genetically predicted OA showed a significant positive association with GORD (OR=1.26, P=5e-05) but not PUD or IBD.
- GI disorders did not demonstrate a causal association with OA.
- OA patients had increased NSAID (OR=1.45, P=0.001) and opioid use (OR=1.77, P=2e-05).
- Opioid use, but not NSAID use, significantly increased GORD risk (OR=1.43, P=5e-09).
- The OA-GORD association was attenuated after adjusting for opioid use in MVMR (OR=1.20, P=0.038).
Conclusions:
- Osteoarthritis (OA) is causally associated with an increased risk of gastroesophageal reflux disease (GORD).
- Opioid use, commonly prescribed for OA pain, mediates this increased GORD risk.
- Non-steroidal anti-inflammatory drug (NSAID) use does not appear to mediate the relationship between OA and GORD.
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