Assessing causality between osteoarthritis and gastrointestinal disorders: a Mendelian randomization study
Abstract The association between osteoarthritis (OA) and gastrointestinal disorders was found in observational studies. However, the causality is still elusive. A bidirectional Mendelian randomization (MR) analysis using genome wide association studies data was conducted to assess the causal associa...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-11-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-46767-9 |
| _version_ | 1797630312792981504 |
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| author | Huiqing Xu Jiahe Wei Dingwan Chen Yingjun Li Qing Shen |
| author_facet | Huiqing Xu Jiahe Wei Dingwan Chen Yingjun Li Qing Shen |
| author_sort | Huiqing Xu |
| collection | DOAJ |
| description | Abstract The association between osteoarthritis (OA) and gastrointestinal disorders was found in observational studies. However, the causality is still elusive. A bidirectional Mendelian randomization (MR) analysis using genome wide association studies data was conducted to assess the causal association between OA and gastrointestinal diseases [including peptic ulcer disease (PUD), gastroesophageal reflux disease (GORD), and inflammatory bowel disease (IBD)]. A two-step MR (TSMR) was conducted between OA, gastrointestinal diseases and drugs to explore the mediating effects of non-steroidal anti-inflammatory drugs (NSAIDs) and opioids use. We used multivariable MR (MVMR) analysis to further validate the impact of prescription history on diseases. Results had statistical significance at a Bonferroni corrected P-value below 0.008. We observed that genetically predicted OA had a significant positive association with GORD [odds ratio (OR) = 1.26, P = 5e−05], but not with PUD or IBD. Regarding the other direction, gastrointestinal disorders as exposure had a null association with OA. Using TSMR, OA patients tended to increase the use of NSAIDs (OR = 1.45, P = 0.001) and opioids (OR = 1.77, P = 2e−05), but only the use of opioids increased the risk of GORD (OR = 1.43, P = 5e−09). Further MVMR analysis showed that the adverse effect of OA on GORD was significantly reduced after adjusting for opioids use (OR = 1.20, P = 0.038). This study provides evidence for the causal association between OA and increased risk of GORD, which is partly attributed to opioids use in OA patients but not NSAIDs. |
| first_indexed | 2024-03-11T11:06:36Z |
| format | Article |
| id | doaj.art-738b05da0e4d40ad9ea207178fe6e5c2 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-11T11:06:36Z |
| publishDate | 2023-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-738b05da0e4d40ad9ea207178fe6e5c22023-11-12T12:12:17ZengNature PortfolioScientific Reports2045-23222023-11-011311810.1038/s41598-023-46767-9Assessing causality between osteoarthritis and gastrointestinal disorders: a Mendelian randomization studyHuiqing Xu0Jiahe Wei1Dingwan Chen2Yingjun Li3Qing Shen4School of Public Health, Hangzhou Medical CollegeSchool of Public Health, Hangzhou Medical CollegeSchool of Public Health, Hangzhou Medical CollegeDepartment of Epidemiology and Health Statistics, School of Public Health, Hangzhou Medical CollegeDepartment of Social Medicine and Health Management, School of Public Health, Hangzhou Medical CollegeAbstract The association between osteoarthritis (OA) and gastrointestinal disorders was found in observational studies. However, the causality is still elusive. A bidirectional Mendelian randomization (MR) analysis using genome wide association studies data was conducted to assess the causal association between OA and gastrointestinal diseases [including peptic ulcer disease (PUD), gastroesophageal reflux disease (GORD), and inflammatory bowel disease (IBD)]. A two-step MR (TSMR) was conducted between OA, gastrointestinal diseases and drugs to explore the mediating effects of non-steroidal anti-inflammatory drugs (NSAIDs) and opioids use. We used multivariable MR (MVMR) analysis to further validate the impact of prescription history on diseases. Results had statistical significance at a Bonferroni corrected P-value below 0.008. We observed that genetically predicted OA had a significant positive association with GORD [odds ratio (OR) = 1.26, P = 5e−05], but not with PUD or IBD. Regarding the other direction, gastrointestinal disorders as exposure had a null association with OA. Using TSMR, OA patients tended to increase the use of NSAIDs (OR = 1.45, P = 0.001) and opioids (OR = 1.77, P = 2e−05), but only the use of opioids increased the risk of GORD (OR = 1.43, P = 5e−09). Further MVMR analysis showed that the adverse effect of OA on GORD was significantly reduced after adjusting for opioids use (OR = 1.20, P = 0.038). This study provides evidence for the causal association between OA and increased risk of GORD, which is partly attributed to opioids use in OA patients but not NSAIDs.https://doi.org/10.1038/s41598-023-46767-9 |
| spellingShingle | Huiqing Xu Jiahe Wei Dingwan Chen Yingjun Li Qing Shen Assessing causality between osteoarthritis and gastrointestinal disorders: a Mendelian randomization study Scientific Reports |
| title | Assessing causality between osteoarthritis and gastrointestinal disorders: a Mendelian randomization study |
| title_full | Assessing causality between osteoarthritis and gastrointestinal disorders: a Mendelian randomization study |
| title_fullStr | Assessing causality between osteoarthritis and gastrointestinal disorders: a Mendelian randomization study |
| title_full_unstemmed | Assessing causality between osteoarthritis and gastrointestinal disorders: a Mendelian randomization study |
| title_short | Assessing causality between osteoarthritis and gastrointestinal disorders: a Mendelian randomization study |
| title_sort | assessing causality between osteoarthritis and gastrointestinal disorders a mendelian randomization study |
| url | https://doi.org/10.1038/s41598-023-46767-9 |
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